USA EXPERIENCE: IN-HOUSE PREPARATION: PROSPECTS AND PROBLEMS

Abstract

Adoptive Cellular Therapy (ACT) is transitioning from experimental to standard of care. Limited specificities of chimeric antigen receptor T cells (CAR-T) are licensed drugs, with commercial products selling for ∼400,000 USD. Tumor infiltrating lymphocytes (TIL) can target multiple cell surface and intracellular tumor antigens. TIL have not been commercialized, due to complex logistics and cost. Our objective is to leverage a single standardized platform (Miltenyi Prodigy) for in-house ACT.We currently manufacture CD19 CAR-T under an FDA IND and are developing a virtually identical TIL protocol minus the lentiviral vector. TIL are manufactured from malignant pleural effusions rich in immune infiltrates. CD4+ and CD8+ cells are enriched and activated with anti-CD3/CD28 beads. CAR-T are transduced, and both CAR-T and TIL are expanded (IL-7/IL-15) for 5 days. The product is infused fresh, avoiding losses associated with cryopreservation and thawing.Developing and validating release tests (absence of replication competent virus, vector copy number, chimeric antigen receptor expression, endotoxin testing) posed an initial challenge. Having completed assay development, our manufacturing process, including release testing, can be performed for less than 1/10 the cost of commercial CAR-T.We expect that the platform that we have validated will be easily transitioned to new chimeric antigen receptor designs and specificities and will likewise be adaptable to TIL manufacture for the wide variety of cancers that metastasize to the pleura of peritoneum. Standardized in-house ACT manufacture may greatly reduce the cost of cellular immunotherapies, making it more widely available to patients.