Adoptive transfer of T-bodies: Toward an effective cancer immunotherapy

Adoptive immunotherapy is a valid treatment for cancer and has been widely practiced in the clinic using antitumor antibodies. Application of the cellular arm of the immune response, although more efficient, has not yet found its way for cancer treatment. The main cause for this lag is scarcity of tumor specific T cells and difficulty to obtain such functional cells from cancer patients. The T-body approach that we have pioneered has been designed to provide answers to these issues. T-bodies are T cells expressing a chimeric receptor composed of an antibody derived antigen recognizing unit in the form of single chain domain linked through extracellular hinge and transmembrane stretches to the cytoplasmic domains of costimulatory and stimulatory molecules. As such the engineered T-body's design takes advantage and combine the specificity and availability of antitumor antibodies with the efficient effector function of T cells. In practice, T-bodies can be prepared from peripheral blood of any cancer patient, engineered ex-vivo to express the chimeric receptor gene on their surface and reinfused back to the patient where it should migrate and accumulate at the tumor site, will undergo specific activation by the tumor antigen and cause selective elimination of the cancer. In this chapter, we describe the preparation of optimal chimeric constructs and ways to safely introduce the chimeric receptor genes to T cells. Most of the research was performed so far in animal models where it showed impressive effects, including complete responses to a large range of cancers. On the basis of this proof of concept many T-bodies have been prepared to human cancers, several of which are being tested for safety in phase I clinical trials.