Abstract
Improvements to T cell culture systems that promote long-term engraftment and function of adoptively transferred T cells will likely result in superior clinical benefit to more individuals. To this end, we recently developed a chemically defined cell culture medium that robustly expands all T cell subsets in the absence of human serum. Using a humanized mouse model, we observed that T cells expanded in the absence of human serum provided durable control of tumors, whereas T cells expanded in medium supplemented with human serum only mediated transient control of tumor growth. Importantly, our new medium effectively expanded more differentiated T cells from multiple myeloma patients in the absence of serum. These patient-derived T cells were also able to provide durable control of B cell tumors in vivo, and this long-term control of cancer was lost when T cells were expanded in the presence of serum. Thus, engineered T cells expanded in an optimized medium in the absence of serum may have improved therapeutic potential.
Highlights
Adoptive transfer of T cells re-directed to tumor-specific antigens by genetic engineering has shown great promise to treat, and, in some cases, cure immune-cell-based cancers
T cells expanded in AIM V grew as well as T cells expanded with AIM V supplemented with human serum for 5 days
We sought to determine whether T cells expanded in 1B2H could perform in vivo as well as T cells expanded using X-VIVO 15 supplemented with 5% human serum—the current medium formulation our group uses for good manufacturing practice (GMP) manufacturing of T cells
Summary
Adoptive transfer of T cells re-directed to tumor-specific antigens by genetic engineering has shown great promise to treat, and, in some cases, cure immune-cell-based cancers (reviewed in Sadelain,[1] Rosenberg and Restifo,[2] and Barrett[43]). Porter et al.[5] observed a strong correlation between T cell persistence and improved clinical responses, suggesting that efforts to enhance persistence of engineered T cells will result in improved clinical responses This clinical success has forged many academic/non-profit partnerships with large pharmaceutical companies to address the challenge of converting the technology and infrastructure required to treat a small number of patients on a phase I clinical trial to a therapy that can be used worldwide to potentially treat up to many thousands of patients yearly.[6] One of these challenges is that human serum is used to expand the genetically engineered T cells.[7] Human serum is expensive; requires adventitious agent testing and could potentially contain emerging infectious agents; varies considerably from lot to lot, requiring frequent screening; and may contain agents harmful for T cell expansion and survival. A T cell manufacturing process that is not dependent on human serum would be an important step to make adoptive T cell therapy less expensive, more consistent, and available to more patients
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