Dalila M. Alvarado-Navarro

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a transformative treatment for patients with relapsed or refractory hematologic malignancies, offering new possibilities beyond conventional transplantation. Since their approval in high-income countries, CAR-T products have demonstrated remarkable efficacy; however, their implementation in low- and middle-income countries (LMICs) remains limited due insufficient infrastructure, complex regulatory requirements and high costs. In some countries, like Mexico, these barriers are particularly pronounced, with limited access to clinical-grade vectors, early phase clinical research programs, and lack of government and private sector infrastructure and funding opportunities. Facing these challenges, there is a substantial patient population with B-cell acute lymphoblastic leukemia, multiple myeloma, or diffuse large B-cell lymphoma, who could benefit from CAR-T therapy. Advances in point-of-care manufacturing within academic settings –particularly the use of closed, semi-automated systems– have demonstrated feasibility in LMICs, by reducing costs and simplifying procedures, while maintaining product quality. These approaches may provide a viable alternative to commercial products, with the potential to lower the economic burden and increase accessibility. Regulatory innovation with the establishment of expert multidisciplinary oversight committees, will also be critical to ensure safe implementation. Ultimately, CAR-T therapy in LMICs is both a scientific and public health opportunity, and its integration into healthcare systems will depend on collaborative strategies that address financial, logistical, and policy barriers. By highlighting our experience, this review underscores the importance of developing locally adapted solutions to expand access to advanced cellular therapies in resource-constrained settings.

PURPOSE: To validate and replicate an automated decentralized CD19 chimeric antigen receptor T (CAR-T) cell manufacturing process from healthy adult volunteers in an academic institution in a middle-income country. METHODS: Healthy volunteers were recruited and underwent leukapheresis with the continuous mononuclear cell (MNC) collection protocol. Clinical-grade CAR-T cell manufacturing was performed in a closed system using a second-generation CD19 vector with 41BB costimulatory domain. Quality control was assessed at different points in the production process with prespecified release criteria including product's aspect, sterility, cell viability, impurity, and quantity. The target dose formulation was 1 × 10 ⁶ /kg viable CAR-T cells per volunteer. RESULTS: Five healthy volunteers were recruited, all donated adequate MNC units, and successfully underwent the manufacturing process. After T-cell culture harvest, the products contained a median CAR-T cell concentration of 16.5 × 10 ⁶ /mL (range, 7.7-22.2 × 10 ⁶ /mL), with a median transduction percentage of 44.7% (range, 39.2%-60.5%) and a median CD3 ⁺ cell viability of 97.7% (range, 90.4%-98.7%). Sterility was maintained throughout the manufacturing process. The quantity of cells harvested per kilogram of body weight was 24.6 MB-CART19.1 cells × 10 ⁶ /kg (range, 9.3-33.1 × 10 ⁶ /mL). The quality was similar in both fresh and cryopreserved units. Dose formulations were 1.1 CAR-T cells × 10 ⁶ /kg (range, 1.0-1.2 CAR-T cells × 10 ⁶ /kg). CONCLUSION: Our study demonstrates an effective methodology with satisfactory and comparable performance to international reports. Point-of-care manufacturing is a feasible alternative to increase access to CAR-T cells in academic centers.

Background Optimization of platelet (PLT) apheresis collection is a priority to satisfy the increasing demand of hemato-oncology patients. We assessed the performance of a plateletpheresis unit supporting hematology patients. Study design and methods This descriptive retrospective study included 561 plateletpheresis collections from 2013 to 2018. For data analysis, descriptive statistics and receiver operating characteristic (ROC) curve were used. A 5-item satisfaction questionnaire was analyzed. Results Ninety percent of the donors were males. The median plateletpheresis time was 89 minutes; its success rate was 92.5%; median donor PLT count was 232 × 10⁹/L, women median PLT count was 247 × 10⁹/L vs 231x10⁹/L in men (P = .017). Seventy-seven percent donors were candidates for a double product and 24.5% were processed; 20.8% of these donors had a weight ≤75 and 79.2% >75 kg, P = .003, and 6.6% were women and 93.4% men, P = .161. Thirty-six of donors had ≥250 × 10⁹/L and 16.8% was processed as a triple product. ROC analysis showed that with donor PLT counts ≥200 × 10⁹/L the sensitivity for obtaining double products was 0.981 and specificity 0.714, with an area under the curve (AUC) = 0.877. The adverse effect rate was 4.3%. Of the potential donors, 6.3% were rejected. The cost of processing single or double products was 430 USD. Comfort and time spent during plateletpheresis were areas for improvement. Conclusion Platelet count and donor weight predicted PLT yield and obtaining double products. Women had higher PLT counts, but no significant difference was found between donor gender and processed products. Assessment of the apheresis unit can help to improve its performance.