Adoptive cell transfer therapy for effective cancer treatment

Cancer is a genetic disease which occurs when damaged DNA sends out faulty signals along biomolecular pathways, causing tumor cells to grow out of control. Since the invasion of tumor cells is “home grown” rather than foreign, an immune response is often not effectively triggered. Despite the presence of antigens on growing tumors, the immune response is not strong enough to destroy cancer cells. In addition, tumors deploy several strategies to evade the host immune response, including downregulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumor environment (T. Blankenstein, 2012). The immune system maintains a constant vigil by pursuing bad actors that harm healthy tissues, such as infection or cancer, and then launch an attack to check the threat.

Traditional cancer treatments include surgery, chemotherapy, and radiation therapy. Researchers have long sought to harness the power of the immune system to fight cancers. However, targeting functional immune T cells to the tumor and maintaining these cells in patients remains a challenge. Immunotherapy evolved as an effective approach for cancer treatment since this modality strategically utilizes different components of the patient’s immune system to fight cancer cells (C.R Parish, 2003). Some are designed to recognize cancer tissue as foreign while others attempt to increase the strength of the natural immune response. Additionally, others interfere with the molecular pathways that cancer cells have taken over to sustain themselves. Adoptive transfer of tumor-reactive T cells has emerged as a promising advance in tumor immunotherapy. Adoptive cell therapy (ACT) is a personalized cancer therapy that involves infusion of antigen-specific T cells with anticancer activity (S. A. Rosenberg and N. P. Restifo, 2015).

T cells constitute the building blocks in ACT and these are collected from the patient’s blood and genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs) . The engineered CAR T cells are grown in the laboratory and then infused into the patient. Following infusion, the T cells multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces (J. Maher). Once inside the body, in addition to attacking tumors directly, CAR T cells, release signaling molecules like cytokines, some of which recruit additional T cells to fight the tumor. ACT can thus be viewed as administering “a living drug”. CARs, in essence, are artificial receptors constructed by linking an extracellular single-chain variable fragment (scFv) of a monoclonal antibody to a tumor-associated antigen and intracellular signaling domain. Inclusion of a transmembrane domain to anchor the CAR to the T cell (J.S. Bridgeman et al., 2010), and one or more intracellular signaling domains induce persistence, trafficking and effector functions in transduced T cells. The recognition specificity of T cells is thus directed to desired cell surface tumor antigens. CARs have been developed to target antigenic molecules on various human tumors, including cancers of the breast, kidney, lung, colon, prostate, ovary, skin and pancreas. CAR T cells recognize a variety of antigens such as carbohydrate and glycolipid structures typically expressed on the tumor cell surface in addition to proteins.

Genetic modification of T cells is a quick and reliable process. Clinical trials with genetically modified T cells targeting a variety of malignancies have remarkable responses in patients with advanced cancer (A. A. Al-Khami, 2011). With continued development of ACT, CAR T-cell therapy offers great potential to become mainstream treatment for several types of cancers. Enzo Life Sciences offers a comprehensive list of antibodies for basic research and better understanding of the immune system in health and disease.

Browse all our TechNotes by Interests

Never miss a new TechNote!

Receive our TechNotes as soon as they are published.