I have sponsor, regulatory and IRB permissions/approval to post this blog publicly on social media. I am very excited about this protocol using TILs for breast cancer, colorectal, uveal melanomas, and now also inclusive of cutaneous melanoma, nsclc, head/neck carcinoma. Further details can be found here at the sponsor site and at clinical trials.gov.
Adoptive cellular therapy using autologous tumor-infiltrating lymphocytes (TIL-ACT) has shown promise in the treatment of metastatic melanoma. The mutagenic role of UV radiation in cutaneous melanomas contributes a large burden of expressed neoantigens that increase tumor immunogenicity, making melanoma an ideal candidate for TIL-ACT treatment. A recent meta-analysis of 13 TIL-ACT studies found a pooled overall response rate of 41% and an overall complete response rate of 12% for 410 pretreated patients with advanced cutaneous melanoma. Bulk non-selective TIL-ACT unfortunately has not shown a significant response for epithelial cancers such as breast and colorectal cancers. Uveal melanomas have shown low responses to checkpoint inhibitors and the only FDA approved option of tebentafusp is limited to a select group of patients with a specific HLA type.
The TBio-4101 program, developed by Turnstone Biologics, is focused on not only enriching for relevant neoantigen reactive T cells, but also reducing the number of irrelevant T cells in the TIL product. This is because bystander T cells may have a negative impact on the clinical efficacy of the TIL product. This process is a TIL preparation method designed to produce a neoantive selective TIL product containing tumor-reactive T cells with a diverse neoantigen-reactive TCR repertoire.
The TBio-4101 process starts by performing whole exome sequencing and RNA sequencing on the patient’s tumor and non-tumor (peripheral blood leukocytes) tissues to identify peptides containing tumor-specific mutations. TILs are extracted from the patient’s tumor and then stimulated with peptide-pulsed dendritic cells. The T cells are then sorted based on the expression of two activation markers to create a selected population of tumor neoantigen-reactive T cells, which are then expanded in culture. This process results in a patient-specific T cell product enriched for neoantigen-reactive T cells.
The Orlando Health Cancer Institute is now enrolling patients who have breast cancer, MSS or MSI colorectal cancer or uveal melanoma for adoptive cellular therapy using a neoantigen selective TILs. The protocol has been amended to now enroll Cutaneous Melanoma, NSCLC and Head Neck Carcinoma With the TBio-4101 clinical trial, this cutting-edge treatment has the potential to revolutionize cancer care.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.