Cancer immunotherapy is currently one of the most effective approaches to treating patients. In it, cancer cells are fought by the body’s own immune system. Despite clinical success, not all people respond satisfactorily to this type of intervention or, if they do, they only have short-term responses, in addition to many side effects.
But a systematic review of the literature, carried out by Rafaela Rossetti, a doctoral student at the Clinical Oncology, Stem Cells and Cell Therapy Program at the Faculty of Medicine of Ribeirão Preto (FMRP) at USP, observed that the combination of two treatments (known as immunological checkpoint and adoptive transfer of genetically modified T cells) may bring promising results.
The article “Combination of genetically engineered T cells and immune checkpoint blockade for the treatment of cancer” was published in January 2022 in the journal Immunotherapy Advances.
“These studies provide lessons on possible approaches to potentiate the performance of immune cells against cancer, making them more resistant to immunosuppressive mechanisms [que reduzem a atividade desse sistema] imposed by the tumor microenvironment”, explains Rafaela Rossetti to Jornal da USP.
T-CARs are T cells genetically modified in the laboratory to produce a type of protein known as CAR (which stands for Chimeric Antigen Receptor) before being cultured and “returned” to the sick person. There are six products approved by the Food and Drug Administration (FDA) – the American drug regulatory agency – for clinical use and available on the market.
“The use of these cells has provided impressive results for the treatment of blood cancer. On the other hand, there are still limitations in their effectiveness against solid tumors”, says Lucas Eduardo Botelho, coordinator of the Gene Transfer Laboratory at the Blood Center of Ribeirão Preto and researcher associate of the Cell Therapy Center (CTC), one of the Research, Innovation and Dissemination Centers (Cepids) financed by the São Paulo Research Foundation (Fapesp).
“The inefficiency is due, in part, to the immunosuppression mechanisms employed by tumors to escape the attack mediated by immune system cells”, says Botelho.
Blocking the immune checkpoint is based on a group of proteins present on the surface of T lymphocytes that need to be activated or inactivated to trigger an immune response. Previous studies, led by Americans and Japanese, have shown that cancer cells stimulate the expression of these proteins (called checkpoints) and their ligands (triggers) in tumor tissue. As a result, tumors “turn off” the immune system, which favors the growth of cancer. The same scientists also demonstrated that the use of antibodies capable of inhibiting the interaction between checkpoints and their ligands restores the antitumor defense response, allowing the reactivation of T lymphocytes.
“This review aimed to assess whether blocking immunological checkpoints would be a promising way to increase the therapeutic efficacy of genetically modified T cells against solid neoplasms”, summarizes Botelho.