Immunotherapy in cancer is not new. It goes back to experiences in ancient Chinese dynasties and, in the modern era, to discoveries of Dr. William Coley who made, in 1891, the first attempts to stimulate the immune system to improve the condition of his cancer patients. With this purpose, he injected a bacterial toxin directly into his patient’s tumor. And that's what immunotherapy is all about: using the potential of our own defense system against infections (immune system) to attack a tumor. Certainly, Coley's theories, viewed with apprehension in his time, were confirmed in the 20th century, when the bacillus Calmette-Guerin (BCG-tuberculosis) administered by intravesical instillation into bladder cancer, started to be used, and is nowadays, one of the standard of care of those tumors.
Speaking in lay terms, we will consider our Immune System as an army. It has all kinds of soldiers: white blood cells (B lymphocytes that fire weapons and produce antibodies, which are the bullets). T lymphocytes (which fight "hand to hand" with tumor cells), dendritic cells (which alert the army about the invasion), and even traitors (regulatory T lymphocytes) that help the tumor to evade those attacks.
Immunotherapy is currently one of the five pillars used to fight against cancer: surgery, radiotherapy, chemotherapy, target therapy and immunotherapy. Modernized by the multiple discoveries performed in the last two centuries (biological products produced by and in cells, for example monoclonal antibodies, cytokines, therapeutic vaccines, CAR-T cells, etc.), we will describe in particular the monoclonal antibodies. It was mentioned that the antibodies were secreted by the B lymphocytes, a subset of the white blood cells. But that can only be accomplished in a living organism, ex-vivo the B lymphocytes can only live for short time and then die.
The Argentinian researcher, Dr. Cesar Milstein, conceived a way to grow and immortalize those B lymphocytes in a laboratory flask, so that they can produce antibodies like a factory whose workers are immortal B cells. Why is the “monoclonal” name added? Because each operator produces only one type of antibody, for example to kill a tumor cell. That discovery, which was not patented because the University in England where Milstein worked did not see for it a practical application, awarded him the Nobel Prize in 1984. Monoclonal antibodies began to be used in cancer immunotherapy, being Rituximab the first to be approved in 1997 for the treatment of lymphomas. Others followed: Herceptin for breast cancer, Avastin to destroy the blood vessels that feed the tumor, etc.
Some years later, Dr. James Allison, an immunologist and Texan researcher, discovered that the immune system has brakes (immune-checkpoints), which prevent an infectious process, for example, from exacerbating the soldiers of the "hand to hand" fight. The brakes naturally limit their actions in order not to damage the rest of the body. But in cancer this brake negatively impacts the patient and benefits the tumor because the T lymphocytes do not attack it. Allison deciphered the mechanisms of that brake and blocked it, by using a specific monoclonal antibody against the CTLA4 molecule, which just helps to lift the foot off the brake, stimulating the lymphocytes to attack the tumor. That is the reason for his Nobel Prize: "discovery of a therapy for cancer, inhibiting the negative immune-regulation". In other words, lift the foot of the brake that prevents the soldiers from attacking. It is a form of immunotherapy that uses monoclonal antibodies to stimulate the immune system itself to destroy the tumor. Its toxicity is lower than other therapies and gives better clinical responses. And since it does not attack cells of a particular tumor, it can be used in any type of tumor, alone or in combination with other established therapies.
Hence, the "Argentine connection": if Milstein had not discovered his monoclonal antibodies, perhaps Allison would have needed another tool to activate the T lymphocytes.
Our laboratory of Monoclonal Antibodies, which I direct, located at the Department of Immunology (Chair Dr. James Allison) of the University of Texas - M.D.Anderson Cancer Center (UT-MDACC), generates "custom-made" monoclonal antibodies: some to be used in therapy, others for basic research, discovering mechanisms to stop the growth of a tumor, or to test the in vitro concept of a potential future therapy. We collaborate with Dr. Allison developing monoclonal antibodies for some of his current projects. We also collaborate with many other researchers of the institution and other universities or private institutions and companies,
My 30+ years of experience in Immunotherapy was in part acquired in Argentina working at the Leloir Institute. In 1987, I received direct training from Dr. Milstein on the methodology for the generation of monoclonal antibodies. I joined UT-M.D.Anderson in 2002 and recently, together with three colleagues, I co-authored the patent of a monoclonal antibody against another of those immune-checkpoints of the immune system, the OX40 molecule. The anti-OX40 antibody was licensed by the UT-MDACC to GSK (Glaxo) and started in 2015 a phase I clinical trial in patients with different tumor types.
Since May 2018, invited by the president of the Argentina - Texas Chamber of Commerce (ATCC) Ariel Bossio, I am part of the board, as an advisor for the Biotechnology and Biomedicine fields. My main objective is to organize events related to these areas of expertise, to facilitate visits by prominent personalities from the scientific and/or medical fields between Argentina and Texas, as well as to promote the exchange of students included in the aforementioned specialties. Obtaining funds from pharmaceutical companies or entrepreneurs, with an interest in this area of knowledge, would help to accomplish these achievements. Potential starting point for attracting companies from Argentina to establish headquarters in Texas, where about 99,000 people work in fields related to various aspects of biological sciences and biotechnology and with an estimated raising number of 360,000 new jobs in the field in the near future.
Laura Bover, PhD
Director Monoclonal Antibody Core Facility
University of Texas M.D.Anderson Cancer Center
Associate member of The University of Texas Graduate School of Biomedical Sciences at Houston
Immunology Department/ Genomic Medicine Department