Genetically Engineered T Cell Immunotherapy for Gliomas and Other Solid Tumors

Cell-based therapeutics, once very popular, were relegated to background mode because of the seemingly complex and highly technical nature of producing the cells at specialized facilities. However, they once again are emerging as promising biomedicines with the potential to substantially impact cancer. The resurgence in adoptive immunotherapy comes with renewed interest in our ability to endow cells with novel attributes by genetic modification. We now have techniques at our disposal to enable the creation of designer therapeutics since the T cells now are handled beyond simple manipulation with growth factors. For cellular immunotherapies, T cells can be expanded and manipulated ex vivo prior to adoptive transfer into the host to achieve a novel immune function and with signaling capability. Also, genetic engineering of T cells has been successfully implemented to redirect the specificity of cytotoxic T lymphocytes towards tumor-associated antigens without MHC restriction. Over 70 Investigative New Drug applications are listed on the Food and Drug Administration maintained website www.clinicaltrials.gov that involve genetically engineered T lymphocytes or T cells endowed with chimeric antigen receptors. While the majority of these trials focus on treatment of hematopoietic diseases generally involving B cells, here, we focus on the description of clinical trials currently testing these modified T cells in patients with solid tumors and even more specifically, for those involving treatment of primary malignant brain tumors.

Keywords: Adenocarcinomas, adoptive immunotherapy, adoptive transfer, astrocytomas, cellular therapy, chimeric antigen receptor, CTL, cytotoxic lymphocytes, gliomas, human leukocyte antigens, immunotherapy, immunotherapy, major histocompatibility complex, melanoma, prostate cancer, solid tumors, T cell receptor, tumor associated antigens.