Principal Investigator Darrell Irvine
Co-investigators Daniel Anderson , J Love , Jianzhu Chen , Paula Hammond , Robert Langer , K Wittrup
Project Website http://web.mit.edu/ki/research/immune.html
Although cancer cells are derived from normal tissues, the changes they undergo should be sufficient for the immune system to recognize and destroy them. In fact, many nascent cancers may be destroyed by the immune system before they develop. The fact that cancers do develop implies that either the immune system fails to recognize the alterations that give rise to cancer or that cancer cells are actively evading the immune response. We are exploring in depth the relationship between the immune system and cancer in animal models and human tissues to understand and overcome the failed immune response as well as to create therapeutic antibodies through state-of-the art protein engineering methods.
Cancer cells are fundamentally different from normal cells; therefore, the immune system ought to be able to recognize cancer cells as foreign and destroy them. Clearly, however, either the immune system is not equipped to recognize the changes that occur in cancer, or else tumors evolve mechanisms to elude the immune response. Believing that the immune system can play a role in the fight against cancer, a team of immunologists and biological engineers are exploring how tumors evade immune recognition and to develop methods to overcome these mechanisms.
The goal of this area is to engineer the immune system to fight cancer. The body's immune system is built to detect and destroy bacteria, viruses, and other pathogens that infect us. It is designed on the principle of distinguishing "self" from "non-self" and eliminating that which is foreign.
By virtue of the mutational and other alterations that underlie their development, cancer cells become fundamentally different from normal cells. In principle, therefore, the immune system might be able to recognize cancer cells as foreign and destroy them. However, the fact that cancers develop in the face of this immune surveillance indicates either that the immune system is not equipped to recognize the changes that occur in cancer or that tumors evolve mechanisms to evade the immune response. These mechanisms likely explain the failure of several clinical trials conducted over the past decade to use cancer vaccines and other strategies to stimulate the immune system to treat cancer.
Based on the conviction that the immune system can be a powerful ally in the fight against cancer, we are assembling a team of immunologists and biological engineers to explore in depth the nature of the relationship between the immune system and cancer, both in animal models of the disease and using human patient material. The goal of this work is to understand how tumors evade immune recognition and to develop methods to overcome these avoidance mechanisms.
New insights into the molecular and cellular control of the immune system by cancer cells will pave the way to more effective anti-cancer vaccines and other forms of immunotherapy. These strategies can be perfected using preclinical models and, working with clinical collaborators, then tested in cancer patients. This program will also develop new approaches to produce and optimize therapeutic antibodies using state-of-the-art methods in protein engineering.