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