The Hyperthermia Research Laboratory in the Division of Oncology at the University of Texas Medical School studies whole body hyperthermia, also known as thermal therapy, for cancer treatment. The goal is to establish underlying principles in order to permit development of effective clinical treatments. Most of our laboratory studies are carried out in suitable in vivo models, with in vitro techniques applied as needed to support and analyze the in vivo work. Over the past 25 years, our laboratory has concentrated on three main areas:
- development of safe thermal therapy regimens
- the ability of hyperthermia to enhance the action of chemotherapy drugs
- aspects of tumor biology affected by hyperthermia.
Our laboratory has developed safe protocols for heating of the whole body. Rather than heating small regions such as limbs or individual tumors, our goal is to target metastatic tumors, those initially undetectable, and too often deadly, cancers that spread around the body. We have shown that prolonged fever-range whole body hyperthermia (FR-WBH) is effective and much less dangerous than higher temperature hyperthermia previously believed to be necessary for anti-tumor effects. We have documented synergistic enhancement of tumor cell kill between fever-range whole body hyperthermia and chemotherapy drugs such as cisplatin, carboplatin, oxaliplatin, adriamycin, 5-FU, doxorubicin, gemcitabine and irinotecan. We have also shown that the relative timing of FR-WBH and drug administration is critical to both the efficacy and the toxicity of the treatment. This knowledge has been translated into a number of successful clinical protocols. In other work, we have shown that FR-WBH can increase the leakiness of tumor blood vessels causing increased delivery of liposomes, small fat bubbles that are used to package chemotherapy agents for delivery to tumors.
As a result of some of these studies, we came to the realization that FR-WBH may be an important aid to making gene therapy work against cancer. Gene therapy seeks to put all, or part of, a gene into diseased cells to either correct faulty genes, or to cause the introduced genetic material to make substances or respond to administered substances that kill the diseased cells, especially cancer cells. Presently, the main problems are that not enough effective genetic material can be delivered to the target cells to cause tumor kill, or that adequate delivery can only be achieved by direct injection into accessible tumors or through potentially dangerous viruses. We believe that FR-WBH could be used to achieve systemic, whole body, non-viral, gene therapy because it can (i) increase delivery of non-viral gene carriers to tumors, (ii) increase the incorporation of the injected genetic material into tumor cells resulting in increased expression of the corresponding protein, and (iii) induce immune cells to attack the tumor. Our initial experiments with FR-WBH and a novel form of suicide gene therapy were promising, though much work still needs to be done before the methodology can move into the clinic.
FR-WBH can also stimulate the body's immune system to fight cancer. We have seen evidence of this in a breast cancer model when thermal therapy follows 24 hours after a low dose of oxaliplatin chemotherapy. In 50% of cases there is a complete immunologic cure such that the animals are immune to rechallenge with the same tumor and go on to live out a normal life-span. The mechanism of this remarkable response is not clear, but we are investigating the nature of the curative immune response and the conditions under which it occurs.