ANTIBODY-CYTOKINE FUSION PROTEINS TO TREAT CANCER
Immunotherapy has revolutionized the landscape in cancer treatment. Unlike traditional treatments such as chemo- or radio- therapy, immunotherapy harnesses the body’s own immune system to recognize and eliminate cancer cells. As a result, immunotherapy assures longer protection for cancer patients while reducing side effects observed with standard treatments which indiscriminately kill both healthy and malignant cells.
T-lymphocytes (T-cells) and Natural Killer (NK) cells are cells of the immune system that play a fundamental role in eradicating cancer. These immune cells feature potent cytolytic activity and when activated, can release cytotoxic molecules (granzymes and perforins) killing cancer cells.
Immunotherapy aims to exploit the aforementioned and other known mechanisms to direct and/or potentiate immune cells against malignant cells.
Conventional treatments directly kill both cancerous and healthy cells in rapid proliferation while immunotherapy stimulates the host immune system which subsequently fight cancer. One of the main advantages of immunotherapy relates to the generation of a long- lasting immune protection which lacks with chemo- or radiation therapies.
During my doctoral studies I have focused on the use of monoclonal antibodies fused to pro-inflammatory cytokines to treat cancer. Antibody-cytokine fusion proteins (also called immunocytokines) are composed by two moieties. One moiety consists of an antibody engineered to target the tumor tissue while the second moiety is a pro-inflammatory cytokine. Cytokines are naturally produced proteins by our organism that have the capacity to boost immune cells including T- and NK cells, important to fight cancer.
Conjugating cytokines to antibodies offer a strategic advantage in cancer treatment compared to conventional cytokine therapy (the natural untargeted cytokine). The efficacy of a targeted delivery approach relies on (i) increased concentration of the payload (i.e. cytokine) at the tumor site, (ii) enhanced activity at the site of disease and (iii) reduced systemic toxicity.
In case you are curious to know more about immunotherapy, the different treatment options and the results I have obtained during my PhD, here’s a copy of my Thesis or you can take a look at the Publications section.
At early time points both the untargeted and targeted cytokine distribute systemically in the body after intravenous administration. At later time points the untargeted recombinant cytokine is rapidly excreted due to a lack of selectivity. Whereas cytokines conjugated to antibodies selectively accumulate at the tumor site enhancing and prolonging anti-cancer activity while sparring healthy tissues.