Cancer Antigen Discovery Program

Cancer antigens are molecules produced by cancer cells that are recognized by components of the body’s immune system, and which can act as targets for antibody therapies or cancer vaccines. LICR scientists cloned the first human cancer antigen, and through the Antigen Discovery Program, have identified a significant number of all known cancer antigens.

Introduction

One of the obstacles in treating cancer is the fact that tumor cells appear to be almost identical to normal cells. Conventional chemotherapeutic drugs are unable to differentiate between cancer cells and normal cells, and most of the side-effects caused by these conventional therapies result from normal cells being destroyed along with the cancer cells. However the body’s own immune system is able to specifically distinguish between normal and cancer cells by recognizing cancer antigens displayed on the tumor cell’s surface. The pioneering work of LICR scientists has paved the way for the development of therapeutic cancer vaccines and antibodies that target cancer antigens, and thus harness the immune system to control the spread of cancer.

Cancer Antigens

Antigens are molecules that can be recognized by antibodies or T cells of the immune system either in the forms of an intact molecule, or as smaller, processed fragments.

Cancer antigens fall into several different categories:

  • Differentiation antigen - a molecule expressed by one particular tissue-type, and also by cancer cells derived from that tissue-type. For example, the tyrosinase and Melan-A/MART-1 antigens, discovered by LICR scientists, are expressed in normal skin melanocyte cells, and in most melanomas, but not other cell types in the body.
  • Mutation and splice variant antigens - alterations in the DNA sequence of a gene frequently result in differences in the gene’s protein sequence when the mutation alters one or more amino acids in the protein. An alteration in the messenger RNA (mRNA) sequence (transcribed from the DNA sequence) may cause the mRNA to be spliced differently, producing different forms of the protein. For example, the NY-CO-38 antigen discovered by LICR scientists, has four splice variants, each of which has a different tissue expression.
  • Overexpressed/amplified antigen - a protein that is overexpressed in a cancer cell compared to a normal cell. For example, LICR investigators have discovered that normal epidermal growth factor receptor (EGFR) can be distinguished by a specific targeted antibody when overexpressed.
  • CT antigens - proteins expressed only in normal ‘germline’ tissues (testis, placenta, and embryonic and fetal ovary) and in cancer cells. Because germline cells do not express major histocompatibility complex (MHC) molecules, the cells are unable to present antigens on their surface, thus a cancer therapy would not target these normal cells. The NY-ESO-1 antigen, discovered by LICR is a CT antigen; it is expressed in testis, in a variety of tumors such as melanoma, breast, ovary, prostate, bladder, sarcoma, and lung.
  • Viral antigens – viral proteins are expressed in infected human cells and these viral proteins, or the peptide fragments resulting from the processing of the proteins, are presented to, and recognized by, the immune system. LICR investigators have identified, and are characterizing antigens that are generated when humans are infected with certain types of human endogenous retroviruses (HERVs), which are though to be etiological agents for several cancers.

The Antigen Discovery Program has two components:

Cancer Antigen Identification

The identification of tumor-associated antigens as the first step for developing cancer vaccines. The International SEREX Program is an essential part of this component.

Cancer Antigen Characterization

To fully investigate and understand the antigen’s expression and the frequency and specificity of the immune response to the antigen.