CAR T-Cell Therapy: Current Practice and Future Solutions to Optimize Patient Access

Abstract: Chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in treating hematologic malignancies. There are currently three CD19-directed cellular therapy products approved by the Food and Drug Administration available to treat relapsed or refractory lymphoid malignancies. Though the current models are promising, challenges remain for patient access, such as the high product price, long production times, among others. With demand increasing for CAR T-cell therapy, innovation is required to target this growing population. This review article will address these clinical and financial challenges and provide solutions to optimize CAR-T cell therapy’s framework toward expanding access.   

Key Words: CAR T-cell therapy, lymphoma, multiple myeloma, acute lymphoblastic leukemia, barriers; access, cost-effectiveness

Chimeric antigen receptor (CAR) T-cell therapy and other engineered cellular therapies are revolutionizing the therapeutic landscape for hematologic malignancies.¹ There are currently three CD19-directed autologous CAR T-cell products approved by the Food and Drug Administration (FDA), namely axicabtagene ciloleucel (axi-cel; Yescarta), tisagenlecleucel (tisa-cel; Kymriah), and brexucabtagene autoleucel (brexu-cel; Tecartus), for the treatment of relapsed or refractory (R/R) lymphoid malignancies. In 2017, tisa-cel was first approved to treat R/R B-cell acute lymphoblastic leukemia (B-ALL).^2,3 Later, axi-cel (2017) and tisa-cel (2018) were approved to treat R/R aggressive large B-cell lymphomas.⁴ More recently, brexu-cel was approved in 2020 for the treatment of R/R mantle cell lymphoma.⁵ Lisocabtagene maraleucel (liso-cel), another CD19-directed CAR T-cell product, has shown promising response rates and was recently approved in February 2021 for the treatment of R/R large B-cell lymphoma.⁶ CD19-targeted CAR-T cell therapies have demonstrated efficacy and are being investigated for treating R/R indolent B-cell lymphomas like chronic lymphocytic leukemia (CLL), follicular, and marginal zone lymphomas.^7,8 B-cell maturation antigen (BCMA) targeted CAR T-cell therapies have shown striking responses and durable efficacy in treating R/R multiple myeloma (RRMM).⁹ Advances in cellular bioengineering are leading to novel cellular therapies being investigated across clinical trials in solid tumors and hematologic malignancies.

Cellular immunotherapy approvals have been transformative in offering a potentially curative option in patients with R/R B-ALL and aggressive B-cell lymphomas; however, these autologous engineered cell therapies present several challenges: cost, access, production, administration, and management of unique immune effector cell (IEC)-related toxicities. Compared to other oncologic drugs, these cellular therapies are priced expensively, ranging from $373,000 to $475,000 per dose, with additional costs levied from hospitalization and supportive care, posing restrictions on coverage and reimbursement. The high cost leads to concerns on universal access and appropriate utilization for patients.¹⁰ Currently, FDA-approved CAR T-cell therapies require experienced clinical teams, most of whom routinely perform hematopoietic stem cell transplantation, who can apply effective quality processes to ensure safe and reliable administration. The global clinical experience with commercially available agents is rapidly growing, which provides an opportunity to analyze current-day challenges about safety, value, economics, and access to effectively implement the next generation of cellular therapies.

This review presents the current state of approved CAR T-cell therapies for hematologic malignancies, clinical and financial barriers, and a framework proposal to expand future access.

Clinical Outcomes of Approved CAR T-Cell Therapies

All three FDA-approved CD19-directed cellular therapies result in higher response rates and improved overall survival (OS) compared to traditional salvage chemotherapies for difficult-to-treat patient populations. These second-generation CAR T-cell constructs primarily differ in their costimulatory domains (tisa-cel and liso-cel [4-1BB based] and axi-cel and brexu-cell [CD28 based] CARs).

In the phase 2 ELIANA trial, among 75 patients (age range: 3-23 years) with R/R B-ALL who received tisa-cel, the overall remission rate at 3 months was 81% patients achieving minimal residual disease (MRD) negative remission. Respectively, the estimated event-free and OS at 12 months was 50% and 76%. Postmarket research from the Center for International Blood and Marrow Transplant Research (CIBMTR) confirmed these findings, with 89% of 96 patients achieving complete responses (CR) 6 months after tisa-cel therapy. Cytokine release syndrome (CRS) occurred in 77% of patients, and 48% received tocilizumab, an anti-IL6 antibody. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 40% of patients and was managed with supportive care.² However, despite impressive response rates of about 70% to 90%, durability of these responses has unfortunately been low in adult R/R B-ALL. More than half of patients relapsed within a year of therapy, if not consolidated with an allogeneic stem cell transplant.¹¹

In the phase 2 JULIET trial, among 93 patients with R/R large B-cell lymphomas who received tisa-cel, the best overall response rate (ORR) was 52%, with CR in 40% of patients. The 12-month relapse-free survival for the whole study group was 65% and 79% in patients achieving a CR. The incidence of CRS was 58% (grade 3-4: 23%), and ICANS was 21% (grade 3-4: 12%).⁴ A subsequent CIBMTR real-world analysis supported these findings.¹²

Axi-cel was evaluated in the phase 2, multicenter, ZUMA-1 trial in 101 patients with R/R high-grade B-cell non-Hodgkin lymphomas (NHL; diffuse large B-cell lymphoma [DLBCL], primary mediastinal B-cell lymphoma, transformed follicular lymphoma).³ The ORR rate was 83%, with a CR rate of 58%. The median duration of response was 11.1 months, median OS was not reached, and median progression-free survival (PFS) was 5 to 9 months. Grade 3-4 CRS occurred in 12 (11%) patients and grade 3-4 ICANS in 35 patients (32%).¹³ A postmarket use outcomes analysis of axi-cel was conducted among 295 patients from 43 US centers by the CIBMTR. The best response and toxicity rates were comparable to the registrational ZUMA-1 trial despite having a larger proportion of older patients, patients with transformed or double-hit lymphoma, and patients with worse performance status.¹⁴ Several other CAR T-cell consortia have also reported real-world experiences with axi-cel and tisa-cel, with efficacy and toxicity similar to the pivotal trials.^15,16

In the TRANSCEND NHL 001 trial evaluating liso-cel (autologous CD19-directed CAR T-cell product with equal target doses of CD8⁺ and CD4 + CAR + T cells) in R/R aggressive NHL, of the 256 patients included in the efficacy-evaluable set, ORR was 73% and CR 53%. Grade 3 or higher CRS and ICANS were reported in 2% and 10% of patients, respectively. Thus, this product’s toxicity and efficacy profile appears favorable and has become the latest CD19-directed autologous CAR-T product to be approved by the FDA.⁶

In phase 2, ZUMA-2 study, on the intention-to-treat analysis in 74 patients with R/R mantle cell lymphoma, brexu-cel showed an ORR of 85% and CR of 59%. At a median follow-up of 12.3 months, 57% of patients were in remission. At 12 months, the estimated PFS and OS were 61% and 83%, respectively. Grade 3 or higher CRS and ICANS occurred in 15% and 31% of patients, respectively⁵ (Tables 1 and 2). 

In the phase 2 KarMMa study evaluating a BCMA-directed CAR T-cell product, idecabtagene vicleucel (ide-cel, BB2121) in R/R myeloma patients, ORR was 73%, CR rate was 33%, and median PFS was 8.8 months. The median duration of response was 10.7 months among all responders and 19 months among those achieving CR or stringent CR. Based on this data, FDA has granted priority review for ide-cel in patients with RRMM who have failed three prior therapies, including a proteasome inhibitor, immunomodulatory agent, and a CD38 monoclonal antibody.¹⁷

Value and Cost-Effectiveness of CAR T-Cell Therapy

Due to the high product price of >$350,000 for a single cell therapy infusion, several studies have attempted to analyze the cost-effectiveness of approved CD19-directed CAR T-cell therapies in R/R lymphoid malignancies. However, these studies are limited by the lack of randomized trials, short-term follow-up data, and cost-effectiveness studies from published phase 2 CAR T-cell trials.¹⁰

In 2018, the Institute for Clinical and Economic Review (ICER) analyzed CAR T-cell therapies in R/R B-ALL (tisa-cel) and DLBCL (axi-cel). Despite higher costs, gains in life years and quality-adjusted life-years (QALYs) were higher for CAR T-cell therapies. The incremental cost-effectiveness ratios (ICERs) were $46,000 and $136,000 per QALY gained with CAR T-cells compared to chemotherapy in B-ALL and DLBCL, respectively.¹⁸

Tisa-cel in pediatric R/R B-ALL, with a projected 40% 5-year relapse-free survival, increased life expectancies by 12.1 years and cost $61,000 per QALY gained. However, with lower relapse-free survival rates, a price reduction to $200,000 to $350,000 would be needed to meet the $100,000 to $150,000 per QALY willingness-to-pay threshold.¹⁹ Axi-cel in R/R DLBCL, with a projected 40% 5-year PFS, increased life expectancy by 8.2 years at $129,000 per QALY gained. With a 35% 5-year PFS, tisa-cel increased life expectancy by 4.6 years at $168,000 per QALY gained. Price reductions to $200,000 to $250,000 would allow both products to cost less than $150,000 per QALY, even with PFS projected at 25%.²⁰

Medicare claims analysis showed that the 177 patients (median age: 70 years), with more than 50% patients having >1 comorbidity undergoing CAR T-cell therapy for R/R large cell lymphomas, spent 17% less time in the hospital following CAR-T therapy compared to before. The total number of emergency room visits was reduced by 50%. Overall health care costs, excluding the cost of CAR T-cell therapy, were 39% lower in the 6 months after therapy. Patient costs per month were $9749 pre-CAR T-cell therapy and $7121 post-CAR T-cell therapy, representing a 27% decrease in expenditure.²¹ These studies did not account for the potential gain in societal value from long-term success through transformative CAR T-cell therapies that could enable children and young adults to have sustained, productive employment.^10,22 Alternative payment models with price modulation could thus aid in increasing the cost-effectiveness of CAR T-cell therapies. 

Patient-Reported Outcomes

Patient-reported outcomes (PROs), with core domains like physical functioning, disease-related symptoms, and symptomatic adverse events, are essential to assess the impact of novel therapies on symptom burden and health-related quality of life (HRQoL). Since 2014, several prospective trials are incorporating validated PRO instruments in the CAR T-cell arena to capture cognitive function and financial toxicity in patients. Preliminary data suggest that patients undergoing CAR T-cell therapy experience fewer physical side effects in the short term and do not have a more significant decline in QoL measures compared to patients undergoing autologous or allogeneic stem cell transplant.²³ Delayed side effects of CAR T-cell therapy are currently unknown. A proposed approach would be to capture PRO with measures like the PROMIS (Patient-Reported Outcomes Measurement Information System) at baseline before lymphodepleting chemotherapy, weekly in the acute phase for the first 30 days, and monthly for the first year after CAR T-cell therapy to identify late cognitive deficits or autoimmune disorders.²⁴

In the ELIANA trial, an improvement in patient-reported QoL measured with the Pediatric Quality of Life Inventory (PedsQL) and European Quality of Life-5 Dimensions questionnaire (EQ-5D) was demonstrated at 3- and 6-months for pediatric and young adults with R/R B-ALL.²⁵ In a single-center experience on axi-cel in R/R DLBCL, though most patients reported low-grade symptoms at 90 days, QoL and neurocognitive measures did not deteriorate over time.²⁶ In a long-term follow-up analysis of the JULIET study, patients who achieved a CR or partial remission to tisa-cel had sustained meaningful improvements in HRQoL at 12 and 18 months as determined using two validated instruments: Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and Short Form-36 (SF-36) Health Survey.²⁷ Similarly, a significant proportion of patients responding to liso-cel were shown to have an improvement in HRQoL measures at 6 and 12 months using the European Organization for Research and Treatment of Cancer QoL questionnaire C30 (EORTC QLQ-C30).²⁸

In a study from the Fred Hutchinson Cancer Center, PROs were analyzed in 40 long-term survivors
after treatment with CD19-targeted CAR T cells. Overall neuropsychiatric outcomes among survivors were favorable. However, nearly 50% of patients reported at least one clinically meaningful negative neuropsychiatric outcome (eg, anxiety, depression, or cognitive difficulty). Younger age, pre-CAR T-cell anxiety or depression, and immune effector cell-associated neurotoxicity syndrome (ICANS) are risk factors for long-term neuropsychiatric problems in this patient population. Thus, a significant number of patients could benefit from mental health services before and after CAR T-cell therapy.²⁹

In summary, long-term data on PRO and HRQoL from engineered cellular therapy needs to be systematically captured and analyzed in the real world. This will aid in accurate assessment of value for expanding the field in the future.

Clinical Administration and Challenges of Current Autologous CAR T-Cell Products

The current day mechanism for delivering commercial FDA-approved autologous CAR T-cell products is a complex and labor-intensive process. The process involves patient identification and referral, review of insurance coverage and authorization, eligibility assessment and disease status work up, leukapheresis, centralized CAR T-cell manufacture, product shipment, lymphodepleting chemotherapy, CAR T-cell infusion, and ensuing clinical care for the management of short- and long-term toxicities. Close coordination between several teams (ie, primary oncology care team, apheresis, manufacturer, cell processing lab, intensive care unit, and allied medical specialties) is quintessential for safe, reliable manufacturing and delivery of cellular therapies. There are published guidelines in the United States and Europe to aid CAR T-cell treatment centers to develop standard operating procedures for the safe delivery of IEC therapies.^30-32

Currently, the care of patients needing CAR T-cell therapy in the United States is restricted to centers with Foundation for the Accreditation of Cellular Therapies accreditation for administering IEC therapies. Payers mainly drive this requirement as it reassures other stakeholders, including patients, that experienced centers provide these complex therapies with appropriate quality checks.

We propose potential interventions to modify and eliminate barriers for appropriate utilization and fair, universal access to approved CAR T-cell therapies. We will focus primarily on modifiable factors: scientific advances in cellular therapeutic design (allogeneic CARs and off-the-shelf products), strategies to simplify the manufacture and delivery of cellular therapies, and changes in reimbursement and current financial model (Figure 1). 

Solutions to Improve Access to CAR T-Cell Therapy

CAR T-Cell-Specific Factors

A. Off-the-shelf CAR T-cell therapy. Despite autologous CAR T-cell therapy’s success, we face multiple challenges in this treatment’s large-scale adaptation. Two critical issues have limited utility of autologous CAR T-cell therapy. First, it is a lengthy and logistically cumbersome production process with patients waiting 3 to 5 weeks for CAR-T cell manufacturing. The long production time is often detrimental; often the disease progresses through bridging chemotherapy, and patients can become ineligible for CAR-T cell therapy.³³ Secondly, from a clinical standpoint, not all patients can be candidates for autologous CAR T-cell therapy. For example, patients with R/R diseases are frequently heavily pre-treated and have significant T-cell lymphopenia. This can potentially hamper autologous T-cells’ collection in sufficient numbers and lead to CAR-T cell production failure. “Off the shelf” or allogeneic CAR T-cell therapy provides an efficient and reliable method in the field of cellular therapies while overcoming the logistical challenges. For successful production and delivery of allogeneic CAR T-cells therapy, cells must avoid rejection due to host T-cells’ recognition and lack of alloreactivity to prevent destruction of normal host tissues.³⁴

A significant concern with allogeneic CAR T-cell products is graft-vs-host disease (GVHD). Donor T-cell recognition of host peptide-HLA complex through αβ T-cell receptor (TCR) complex is considered a primary mechanism for GVHD. Examples of approaches include:

Use of αβ TCR-negative cells: gene editing tools like CRISPR/Cas9, zinc finger nucleases, and transcription activator-like effector nucleases (TALEN) are utilized to knock down TCRαβ in donor cells and produce universal CAR T cells

Use of nonalloreactive T cells: virus-specific T cells derived from healthy donors with or without genetical modification or directly loaded with viral peptides³⁵

Over the last few years, there has been a significant improvement in the technology of “off-the-shelf” CAR T-cell therapy, and multiple trials are underway. Studies, like the phase 3 ALLELE (NCT03394365) using non-engineered allogeneic T cells to treat R/R EBV+ post-transplant lymphoproliferative disease, are well poised to be available soon as standard of care. At the 2020 American Society of Hematology (ASH) conference, allogeneic CAR T-cell therapy trials were presented for large B-cell lymphoma and RRMM showing early evidence of safety and feasibility with products available to infuse in a matter of days from time to enrollment on the study.^36,37 These studies also explored the feasibility of outpatient CAR T-cell infusion and show promise for expanded access to therapy.

B. Manufacturing Technology. Autologous CAR T-cell therapy are the epitome of individualized therapy; however, this personalized aspect poses a challenge for large-scale CAR T-cell production. Although biopharmaceutical companies are more adapted to large-volume production of CAR T-cell therapy, it remains a challenge for timely access globally.³⁸

As mentioned earlier, vein-vein time (ie, from collecting T-cells to re-infusion of engineered T cells) can range from 3 to 5 weeks with most of the time involved in T-cell engineering. Various approaches are being evaluated to shorten vein-vein time. One such technique is CliniMACS Prodigy (Miltenyi Biotec), a closed automated system that offers integration solutions where cells are manufactured with closed-tubing pathways and provide “CAR T-cell in a box.” This decentralized approach circumvents the need for extensive infrastructure and resources required for an efficient manufacturing practice facility. Medical College of Wisconsin successfully finished a phase 1/1b study of bispecific CD19.20 CAR T-cell therapy in R/R B-cell lymphoma (NCT03019055) and plan to do a multi-institutional study with a similar approach.³⁹ For CAR T-cell manufacturing, an essential raw material is a viral vector that takes over 2 weeks to manufacture. To further reduce production times and improve CAR T-cell production scalability, companies/institutions are exploring nonviral approaches, eg, transposon/transposase-based system that uses DNA plasmids-based process called electroporation to transfer genes into T cells.⁴⁰ Various genome-editing technologies like TALEN (transcription activator-like effector nuclease), CRISPR-Cas9, and ZFN (zinc finger nuclease) are under investigation to produce allogeneic CAR T-cells. Multiple clinical trials have initiated (NCT03166878, NCT03229876) using CRISPR/Cas9 gene-edited universal allogeneic CAR T cells.

Finally, the use of natural killer (NK) cells engineered to express a CAR is another important off-the-shelf treatment option. Allogeneic NK cells, from a source like cord blood, have been safely administered without the need for full HLA matching. Recently, Liu et al described the safety of anti-CD19 CAR-NK cells derived from cord blood in phase I/II trial in R/R CD19 positive cancers.⁴¹

C. Location of care. The changing landscape of CAR T-cell therapy to be safer and less toxic has allowed outpatient therapy to emerge. Evidence shows that outpatient administration of stem cell transplant leads to a similar or better QoL, PROs, and cost-effectiveness compared to inpatient stem cell transplant.⁴² Recently Bachier et al presented data on 44 patients with R/R large B-cell lymphoma treated in an outpatient setting from three clinical trials: TRANSCEND NHL 001 (NCT02631044), PILOT (NCT03483103), and OUTREACH (NCT03744676). Outpatient administration of CAR T-cell therapy was found to be safe and effective, with 45% of patients remaining outpatient and only 5% admitted to the intensive care unit after CAR T- cell therapy.⁴³ Lyman et al performed an economic evaluation of CAR T-cell therapy by the site of care in patients with R/R large cell lymphoma. They showed a ~$32,000 reduction in total cost when CAR T cells are administered in an outpatient setting.⁴⁴ The ideal candidate for outpatient CAR T-cell therapy infusion is agents with delayed onset of CRS like liso-cel and cilta-cel; however, hospital-based outpatient clinics have successfully performed outpatient CAR T-cell therapy with various types of CAR T-cell therapy products.⁴⁵ Multiple modalities are underevaluation for implementing outpatient CAR T-cell therapy, including virtual monitoring, electronic tablets, and digital monitoring tools for in-home monitoring and evaluation.⁴⁶ Even more than before, with an ongoing pandemic and shortage of inpatient beds and outpatient-based CAR T-cell therapy, it can not only improve access and reduce cost but provide much-needed resources for other patients.

Financial Factors

A. Decentralizing CAR T-cell production. The current three FDA-approved CAR T-cell products are primarily manufactured by a pharmaceutical company using autologous T cells. As mentioned earlier, the CAR T-cell manufacturing process to engineer T cells is followed by quality and safety tests before they are shipped back to hospitals to be reinfused into the patients. It is now established that academic medical centers are very well equipped to manufacture CAR T cells⁴⁷ using Good Manufacturing Practice-grade facilities, including novel technologies like Miltenyi Prodigy system or Cocoon^® incubator (Lonza Pharma & Biotech), and provide potentially cheaper and rapid access to CAR T-cell therapy. Decentralizing the CAR T-cell manufacturing has significant advantages: reducing the cost of CAR T-cell production, shortening the time from collection to infusion of CAR T-cell, and the ability to scale quickly without waiting for new large-scale manufacturing plants.

As CAR T-cells are considered drugs, academic centers have to go through a rigorous regulatory approval process to provide CAR T-cell therapy commercially. According to the US Public Health Service Act, human cells, tissues, and cellular/tissue-based products are sorted in two regulatory pathways – Section 351 and 361. The core criteria for “361 products” include a minimal level of cells’ manipulations and their intended use. CAR T-cell therapies are regulated under section “351 product”; hence, they are subject to primarily the same regulatory and premarket approval standards as drugs leading to a significant regulatory burden for an academic center to produce CAR T-cell therapy.⁴⁸ Academic transplant centers have clearly shown their ability to safely manufacture CAR T-cells; besides antigen receptor manipulation, CAR-T therapy shares a similar process to autologous stem cell transplants, which are not regulated through Section 361.

Decentralized manufacturing with a more permissive regulatory landscape is already showing promising results, eg, in Switzerland, hospitals offer CAR T-cell therapies at $150,000 to $200,000, approximately half the US price.⁴⁹ Various options are being proposed to the FDA to reduce cost and overcome the above challenges, like adding a specific clause to Section 361 or creating an exception under 21 CFR §1271.15 for hospital-based CAR T-cell manufacturing.⁵⁰

B. CAR T-cell therapy reimbursement. In the United States, with the current payment model, there is a significant reimbursement gap. Since the first FDA approval of CAR T-cell products in 2017, there has been a slow but steady improvement in reimbursement strategies by the Centers for Medicare & Medicaid Services (CMS). In 2021, CMS is introducing several changes to improve reimbursement for CAR T-cell therapy^51,52:

• CAR T-specific Medicare Severity – Diagnosis Related Group (MS-DRG): this change led to a higher weight of MS-DRG, with an unadjusted base payment rate of $239,929 (compared to $43,094 in 2020)
• New Technology Add on Payment (NTAP): through this option, CMS provides an additional payment to the hospital above the standard MS-DRG payment amount for therapies that qualify for NTAP. In the updated changes, CMS discontinued NTAP status on currently approved CAR T-cell products (Kymriah, Yescarta, and Tecartus) and will not grant NTAP to liso-cel

These new reimbursement guidelines are not adequate for variable patient care cost or even the cost of the product itself. In the United States, providers do not set prices for drugs or treatments. Various national societies, including American Society of Clinical Oncology and ASH, have voiced their support and outlined their position for reimbursing the full cost of CAR T-cell therapy. With many more cellular therapies in clinical trials, it is more crucial than ever to think of innovative payment strategies to maintain access to cellular therapies. Various payment models, eg, milestone-based contracts and outcomes-based agreements, are currently being evaluated for CAR T-cell therapy payment structures and are likely to see growth in their utilization. One such example is Kymriah where, shortly after FDA approval, Novartis announced an optional outcome-based agreement (OBA). In this program, the provider agrees to participate for all eligible patients, regardless of payer, and the provider will not be charged for the product if the treated patient does not achieve anticipated complete remission status within 35 days of CAR T-cell infusion. To bring impactful change and improve access to CAR T-cell therapy, a collaboration between the national organization (eg, American Society of Transplant and Cellular Therapy, European Society for Blood and Marrow Transplantation, Foundation for the Accreditation of Cellular Therapy, Joint Accreditation Committee ISCT – Europe), regulatory agencies (FDA and European Medical Agency), and national payers is crucial.⁵³

Conclusion

The current day utilization of CAR T-cell therapies in clinical settings to treat hematologic malignancies is promising but lacking innovation to meet demands. As outlined, phase 2 trials of approved CAR T-cell therapies in lymphoid malignancies have demonstrated higher response rates and survival compared to traditional chemotherapies. However, despite positive outcomes through gains in life years and higher QALY, treatment with CAR T-cell is still very expensive. Decentralizing manufacturing could lower cost and improve vein-vein time, allowing for increasing access. Furthermore, focus should go toward off-the-shelf products like allogeneic CAR T-cell therapies to improve large-scale adaption and bypass the bottleneck of apheresis. Solutions provided in this article can bridge the gap between demand and patient access to CAR T-cell therapies.

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