Multiple Antibody Panel to treat Esophageal Squamous Cell Carcinoma (ESCC)

Chitra Roy, University of Calcutta

Cancer Immunotherapy work by helping the immune system to function in an efficient manner to fight cancer cells. For the immune system to start its response, it must first be able to identify and differentiate between self-part of your own body and non-self-foreign/antigen. Cancer Immunotherapy is generally divided in two main groups, Active Immunotherapy and Passive Immunotherapy. In active immunotherapies, cancer cells are examined to find the presence of tumour-specific antigens. Its treatment plan involves making the immune system target those antigens, for example, in cancer vaccines and adoptive cell therapy. Whereas passive immunotherapy does not stimulate the immune system and its treatment involves providing manmade immune system components like, cytokines and immune checkpoint inhibitors to fight cancer.

Currently, cancer antigens and neoantigens are making breakthroughs in unlocking a totally new generation of immunotherapy. Neoantigens are markers which are present on the surface of the cancer cells. They arise when tumour cells accumulate mutations by rapidly dividing and multiplying. So, these markers are recognized as ‘foreign’ by our immune system, especially the T-cells, which targets those cancer cells for destruction. Since these neoantigens and cancer antigens are very diverse in nature and their expression vary among individuals, current research focuses a lot on the usefulness of their antibodies as biomarkers. 

Whenever cancer immunotherapy is effective, there is an increasing level of antigens and antibodies in the blood. Using this concept, recently a new technology was reported which could quantitatively evaluate the level of the immune response in cancer cells from a small amount of blood samples. 

The researchers evaluated the usefulness of such antibodies. They collected serum samples from 85 patients with Esophageal squamous cell carcinoma (ESCC) and performed a SEREX method-serological analysis of recombinant tumour cDNA expression libraries, to isolate tumour antigens for cancer immunotherapy combining cDNA library expression with serological typing. The antigens expressed were amplified by PCR. They also sequenced it to confirm whether the correct sequence was inserted in the plasmid. The serum samples which was collected from cancer and healthy patients(control) were also tested for 14 antibodies using ELISA. In addition to studying antibody expression, they also investigated gene mutations and expressions to determine survival rates using cBioPortal and UALCAN. Ultimately, the prognosis of positive and negative antibodies was compared. 

Their studies revealed that patients were positive for all antibodies except for VEGF and reported that antigen-related gene did not have any mutation or amplification, therefore antibody was induced only due to increased gene expressions. In this study only 4 antibodies- LGALS1, HCA25a, HCC-22-5 and HSP70 were induced due to gene over-expression which can be applied as a panel rather than using conventional tumour markers because presence of other antibodies showed no association with disease prognosis. Moreover, a combination of this panel of four antibodies and conventional tumour markers also showed improved positive rates making this a very reliable strategy in near future. 

Also read: Peeking into Portable Eye Examination Kit (PEEK).

Reference: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07466-0

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