Chimeric Antigen Receptor - Clinical Studies Testing Chimeric Antigen Receptor

Clinical Studies Testing Chimeric Antigen Receptor

This method is based on the reprogramming by the vector (for example viral), and chimeric antigen receptor, that redirects them against malignant cell and enables their destruction. There has been interest of sciences in the use of CAR-modified T cell as cancer immunotherapy. In the pre-clinical and clinical trial, there has been a focus upon optimizing in field of structural and signaling.

The first generation of CAR-modified T cell showed success in pre-clinical trial and entered phase I clinical trials. Clinical trials included of ovarian cancer, neuroblastoma and various type of leukemia and lymphoma. The clinical trials showed little evidence of anti-tumor with insufficient activation, persistence and homing to cancer tissue. Some anti-tumor responses being reported in patient with B-lymphoma (treated with alfaCD20-CD3zeta CARs-modified T cell) and neuroblastoma (treated with ScFv-CD3zeta CARs-modified T cell) were reported partial response, stable diseases and remission.

The second and the third generation CAR-modification T cell are capable of delivering enhance of activation signal, proliferation, production of cytokines and efector function of CAR-modified T cell in pre-clinical trial. Both the second and the third generation CAR-modified T cell entering to the clinical trial now. The first clinical trial have shown some promising result. In study with alfaCD19.4-1BB.CD3zeta T cell in patient with chronic lymphocyte leukemia has been complete remission has been ongoing 10 month after treatment. The CAR-modified T cell were found to expand 3-logs in this patient(s), that infiltrated and lysed cancer tissue. Interestingly, a fraction of these cell displayed a memory phenotype of T cell for preventiv tumor relapses. Although, these CAR-modified T cell produced significant therapeutic effect, thein activity lead to life-threatening efect from lysis od the tumor, after 3 weeks the first infusion CAR-modified T cell.

Recently adverse events were reported which highlight the need for caution while using sekond and third generation of CAR-modified T cell. The patient died 5 day after cyclophosphamide chemotherapy, followed by infusion of CAR-modified T cells. The toxicity lead to a clinically signifiant release of pro-inflammatory cytokines, pulmonary toxicity, multi-organ failure and eventual death of the patient. The next problem is off target cytotoxicity, that lead to autoimmune reactions, because most of tumor-associated antigens are expressed on normal tissue.

The great promise of cancer immunotherapy is the cure of tumor without the toxicity of conventional treatments. The pre-clinical and clinical trial of CAR-modified T cell have given hope in cancer therapy. The treatment of cancer of this modified T cell has several advantages: HLA-independent recognition of antigen, broad applicability for many patiens and the rapid deliver of CAR-modified T cell. The successful application of cell will require the identification of target antigen, that are expressed only tumor cell, thereby minimizing the risk of toxicity,

Actual list of tumors antigens and CARs in in-vitro and in-vivo trials,: