Would you, could you drive CARs to point-of-care manufacturing? Yes, you should!

Approximately 45,070 patients worldwide have received chimeric antigen receptor T-cell (CAR T) therapy for hematologic malignancies since regulatory approval of the first CAR T products in 2017.¹ However, the demand for these transformative therapies is significantly higher as numbers of newly diagnosed cases of non-Hodgkin lymphoma and multiple myeloma in the United States in 2025 are expected to be 80,350 and 36,110, respectively.² This supply/demand imbalance is a challenge that will grow as new CAR T therapies are approved for other indications such as solid tumors, autoimmunity, and infection.

There are seven commercially available CAR T products, and each is produced at centralized contract manufacturing organizations located throughout the United States. The ability to deliver an adequate supply is limited by the small numbers of certified manufacturing centers, production slots, and trained staff. The manufacturing process is complex, lengthy (typically 3-6 weeks), and expensive due to the intricate coordination of both material supply and product distribution. Consequently, the per dose prices of CAR T are exorbitant, ranging from $503,580 to $605,404.³ CAR T therapy can cost as much as $1 million or more per patient after adding charges for inpatient stay, toxicity management, and outpatient follow-up.⁴

This combination negatively impacts accessibility to and efficacy of treatment with CAR T. Indeed, long waiting times for delivery of CAR T are associated with increased mortality as seen in multiple myeloma, in which as many as one in four patients die while waiting to receive their CAR T.⁵ For patients who do receive CAR T, the delayed treatment often means patients are receiving CAR T later in their disease course which often diminishes treatment effectiveness and increases toxicities.⁶

Application of a decentralized point-of-care (POC) manufacturing model addresses some of the accessibility issues. POC is usually academic- or hospital-based and mostly used to prepare investigational CAR T. This model removes the expense of and time to ship materials and products to and from a centralized contract manufacturing organization and typically reduces the waiting time for an open manufacturing slot to less than 2 weeks. This results in a 2- to 3-fold reduction in total patients’ waiting time as compared to that with commercial CAR T.⁷ The starting material, a patient’s leukapheresis product, for the POC process is frequently collected within 48 hours of the start of manufacturing and is used fresh, not cryopreserved as is necessary for centralized manufacturing. Similarly, the final CAR T product is frequently infused as a fresh cell formulation rather than cryopreserved for shipping from the centralized contract manufacturing organization to the treatment site. Foregoing cryopreservation saves both time and money and may improve T-cell fitness.

Implementation of automated closed-system manufacturing platforms at POC can further ameliorate the financial toxicity of commercial CAR T. These platforms streamline and standardize the manufacturing process and reduce manual labor, thus cutting the production cost of CAR T to an estimated $78,849 in 2019.⁸ Moreover, automated systems accelerate the process such that the time to final CAR T product is 8 to 14 days.⁷ This makes POC CAR T an attractive option to support patients who cannot wait 3-6 weeks for the treatment due to rapidly progressing disease.

POC manufacturing is practicable, but it requires a substantial financial commitment to: (i) build, validate, and maintain a controlled environment manufacturing space; (ii) purchase and validate manufacturing and analytical quality control equipment; (iii) recruit and train skilled personnel; and (iv) provide quality management oversight. At our institution, the cost to convert and equip a 1,450 square foot space into a cleanroom suite with four ISO7 and two ISO8 rooms was nearly $1.5 million in 2018. Demonstrated efficacy of POC therapies could be helpful to justify the high cost of cleanroom installation.

In this issue of Haematologica, Marcus and colleagues from Chaim Sheba Medical Center (Israel), Memorial Sloan Kettering Cancer Center (MSKCC) (USA), and Rambam Health Care Campus (Israel) directly compare treatment outcomes after patients had received CD19-directed CAR T made locally at Sheba Medical Center or commercially prepared axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel).⁹ A total of 330 patients were included in the analysis, consisting of 94 who were treated at Sheba with locally produced CAR T versus 132 and 104 in the axicel and tisa-cel treated groups, respectively. The number of patients in each cohort is robust and enables meaningful comparisons. Propensity score analysis was used to balance the characteristics of subjects in the groups that received the commercial products versus the locally manufactured product, thereby reducing systematic error. Sheba Medical Center achieved a CAR T manufacturing success rate of 98.8%, which is higher than the rates reported for axi-cel (96%) and tisa-cel (91%).^10,11 Patients treated with locally manufactured CAR T were younger and had a higher frequency of elevated lactate dehydrogenase, primary refractory disease, and higher tumor burden. Even so, non-relapse mortality, overall survival, and progression-free survival in the POC cohort were similar to those of patients treated with commercial CAR T. The vein-to-vein time for POC CAR T of 11 days was significantly shorter than the delivery times for axi-cel or tisa-cel of 38 or 44 days, respectively. This is consistent with the use of POC manufacturing for patients who needed more urgent treatment.

These findings affirm the value of having both central and decentralized options for manufacturing CAR T, enabling an option to be selected based on the patient’s disease characteristics. This report by Marcus and colleagues is an important contribution and timely given the need to increase accessibility to CAR T therapy and the ongoing need for POC manufacturing of investigational immune cell therapies. In addition, POC manufacturing as described in this paper could allow access to CAR T for patients who lack suitable insurance coverage or who need charity care. Advanced cellular therapeutics are here to stay and it is incumbent on its practitioners to find ways to deliver it more efficiently and cheaply (Figure 1). This paper by Marcus and colleagues describes a safe and effective pathway forward.

Figure 1.Image generated by ChatGPT. OpenAI. (December 3, 2025). https://chat.openai.com/

Footnotes

• Received January 14, 2026
• Accepted January 19, 2026

Correspondence

A.P. Rapoport RAPOPO@umm.edu

Disclosures

No conflicts of interest to disclose.

Contributions

KGH developed the conceptual focus of the editorial and drafted the manuscript. APR provided critical revisions and contributed additional literature insights. Both authors approved the final version and accept accountability.

Acknowledgments

We thank NR Varakala and SL Hancock for providing technical assistance and creative input during the development of this editorial.