: Rapid and unrestrained proliferation of Human breast cancer cells
in vitro. The black arrow points to a plastic bead to which the cells adhere.
Although we donít know what exactly is responsible for causing cancer, we do know a bit about how cancer cells continue to divide almost indefinitely. Halting this uncontrolled division of cells (which is made possible by an enzyme called telomerase) is the basis of the new anti-cancer vaccines under development.
What exactly are telomeres??
As you know chromosomes consist of a large number of nucleic acids (Adenine, Guanine , Cytosine and Thymine) arranged in a particular sequence. This sequence, which differs from individual to individual, is responsible for manufacturing proteins in the body.
However, all the nucleic acid sequences do not code for proteins. A large proportion of the chromosome consists of sequences which do not code for any proteins. These parts of DNA, previously called as "Introns" were believed to be useless, and the exact reason for having such redundant pieces of genetic code were not known.
Turning to the subject proper, although the function of introns is still not completely understood, they are no longer regarded as unimportant. The ends of all chromosomes contain specialized repeated sequences of DNA (TTAGGG in humans) called "Telomeres", that serve to maintain the integrity of the chromosome. (It is easy to visualize these sequences as "caps" at the end of the chromosomes)
As a cell divides these "caps" gradually shorten in length. When the "caps" or telomere sequences disappear completely, the inner genetic material is exposed to damage and when that occurs, the cell can divide no more and it dies. In short, the telomeres act like "Biological clocks" that limit the number of times that a cell can divide.
What is the reason then, that cancer cells can divide repeatedly?
The reason WHY the cancer cells do so is still not known. But the mystery of how the cancer cells manage to do so, inspite of the problem of telomere shortening is now beginning to be unraveled.Almost 90% of all cancer cells in humans contain an enzyme called "Telomerase" which helps to replace the lost parts of the telomere, in other words restoring its length. Thus, the protetive "caps" remain intact, the inner genetic material is protected from damage and the cancer cell can divide more times as compared to normal cells.
Most of the newer vaccines being tested now induce a immunological response against telomerase, so that the cancer cells , too , die a "Natural death" due to telomere shortening.
Some of the older vaccines under research , however, work in the same way as vaccines we are familiar with do. These vaccines target specific antigens which seem to be found on the surface of all ( or almost all) cancer cells, thereby inducing an immune response against the cells themselves.
Specific Vaccines under development:
1) Theratopeô ( Vaccine for Breast cancer ) :
Image : Mammogram showing a lobular Ca in the upper region of the breast
Status : Phase III (last phase) of Human trials. This vaccine has been placed on the FDA's (food and drug administration's) "fast track list" for approval.
2) TERT vaccine ( "Universal Cancer
Vaccine " based on telomerase research):
The vaccine causes expression of a specific part of telmorase , called TERT
(or Telomerase Reverse Transcriptase), on the surface of the "dendritic
cells" of the immune system. These dendritic cells then present this
antigen to other cells of the immune system, producing an immune response which
is cell mediated (either Killer-Nk / Cytotoxic T cells.). This immune response
is directed against telomerase and thus halts the rapid division of the cancer
Interesting fact : Both the above
studies use a genetically engineered retrovirus to get the genes coding for TERT
inside the dendritic cells. This is how it works : The RNA of a retrovirus is
modified so that it becomes harmless to humans. The gene coding for TERT is now
integrated into the viral RNA. When this virus is injected into animals/humans , it
infects the bodyís cells (in particular the dendritic cells). The normal
retroviral process now occurs and the proteins coded by the RNA (namely TERT)
are produced. These proteins are recognized by the dendritic cells, setting off
an immune cascade and subsequently, cell-mediated immunity against telomerase.
3) TF / TN Carbohydrate complex vaccines ( older kind of vaccines)
Research currently on at:
Donít be intimidated by the short forms. TF and TN are simply two carbohydrate antigens which are present on the cell surface of many cancer cells. Obviously therefore, these vaccines have nothing to do with telomerase and depend upon inducing an immune response against the cancer cells themselves (Specifically, against the cell memb. proteins)
TN , in particular, has been found in abundance in prostrate cancer cells. The TN cabohydrate complex was also very efficient in inducing an antibody response in mice.
Currently both these vaccines are under clinical trials in humans. Antibody production against the TN antigen has been noted, but the actual clinical effects remain uncertain.
Status : Human trials
Transformation of normal cells into Ca-cells by expression of telomerase :
Non- Profit distributed computing program for Ca- research :
Description of the normal structure of a chromosome :
American Cancer society :