Understanding T-cell activation as a powerful mechanism for fighting cancer

A T-cell is a subtype of white blood cell, also called leukocyte which are the cells of the immune system that are involved in protecting the body against infectious disease and foreign invaders. T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells, by the presence of a T-cell receptor complex (TCR) on the T-cell surface which helps to activate both the cytotoxic T-Cell (CD8+ naive T cells) and also T-helper cells (CD4+ naive T cells), therefore turning them into activated "killers" of foreign invadors. The commonly used binding site for T-cell activation is called CD3 (Cluster of Differentiation 3), a component of the TCR complex, responsible for TCR-mediated signal transduction, activation and tumour-cell killing.

These activated T-cells play a central role in provoking an immune response that does not involve antibodies, but rather involves the activation of the body own immune cells which are these antigen-specific cytotoxic or activated T-cells, and the release of various cytokines and chemicals in response to an antigen - a molecule capable of inducing an immune response on the part of the own patient body. 

In cancer, a newly formed tumour has a tumour antigen which essentially a substance produced in newly formed tumour cells, and which triggers an immune response in the patient. In that sequence, tumour antigens are therefore useful tumour markers in identifying specific tumour cells in specific tumour types.

When a tumour antigen found on the surface of tumours and a T-cell can crosslink with an activating T-cell surface molecule such as the T-cell receptor complex (TCR) via the CD3 function, it can create an “immune synapse” between the target antigen on the tumour cell and the T-cell. This anti-CD3 binding induce (any) T cells to release granzyme and perforin from CD8+ cytotoxic cells, proteins which directly lyse tumour cells, or promote T-cell proliferation (CD8 and CD4 T-cells) and secretion of cytokines (mainly TH1 response, such as IL-2, TNF-α and IFN-γ).

Targeted tumour cell killing is dependent on the presence of the multi-specific cross-linking antibody, and importantly in terms of therapy, this immunotherapy recruits all available T-cells regardless of their actual TCR specificity (i.e. they don't actually need to be cancer targeting T-cells, but just simply T-cells floating around in the blood due to a flu or an occasional infection, all of which become activated as cytotoxic T-cells and are directed to the tumour in order to kill it as that is the cytotoxic T-cell natural function.

Biotecnol Tribody™ molecules do just that. They crosslink T-cells with tumour antigens via the CD3 effector function expressed in the T-cells, in order to kill the tumour.

By clicking this link, you can see a Tribody™ engineered with an anti-5T4 tumour antigen which is expressed in Triple Negative Breast Cancer cells and an anti-CD3 antibody which is specific for T-cells. The anti-5T4 antibody binds the 5T4 antigen expressed by the tumour and the anti-CD3 binds and activates the circulating T-cells,  directing them to the tumour, provoking the lysis of the tumour cells.