Fighting Tumors with Tumors
By Sean Henahan, Access Excellence
Farmington, CT (10/3/97)- An innovative approach to cancer therapy
involving the use of proteins purified from tumor cells may provide more
targeted treatment for cancer patients.
Working with mice in the laboratory, researchers the Center for Immunotherapy
of Cancer and Infectious Diseases at the University of Connecticut School
of Medicine reported promising results when immunizing mice with
heat shock proteins derived from the mice's own tumors.
The researchers injected mice with heat shock proteins purified
from the animals' tumors. This resulted in retarded progression of the
primary lung cancer, melanoma, and colon cancer. The immunotherapy also
reduced metastasis, and prolonged the lifespan of the animals. The effect
on metastatic (spreading) cancers is especially important, as these kinds
of cancers have proven to be among the most difficult to treat.
The approach to immunotherapy of cancer described in the report should
be applicable to virtually all forms of cancer. Heat shock proteins can
be purified from a tumor specimen removed by surgery or biopsy. The versatility
of heat shock proteins in the treatment of cancer derives from their normal
physiological role in cells. These proteins play a role in protein trafficking,
whereby they keep other proteins in their correct shape and location. When
these molecular chaperones are purified from cells, they bring along peptides
derived from other proteins expressed in that cell, providing a molecular
"fingerprint" of the cell's content. Vaccination with the HSP-peptide complexes
purified from cancer cells has the potential to specifically stimulate
the immune system to attack cells bearing those peptides, i.e., the cancer
cells themselves, the researchers note.
"The HSP-peptide complex vaccination is perhaps the first general principle
of immunization which now has shown to be effective against a wide variety
of pre-existing cancers," said Pramod K. Srivastava, Ph.D., of the University
of Connecticut School of Medicine and Principle Investigator for the project.
"Decades of research suggests that tumors are distinct from one individual
to another, with each tumor containing its own unique set of mutations.
The task of identifying each of these mutations in individual cancer patients
-- with the intent of targeting them immunotherapeutically -- is therefore
impractical. In contrast, the process of purifying HSPs is the same for
each patient's tumor and is relatively simple."
Phase I clinical trials, designed to measure the safety of new drugs,
are now underway with a heat-shock protein based-vaccine in patients with
pancreatic cancer. The vaccines are being prepared from individual cancer
patients' tumors. Phase I clinical trials for the treatment of melanoma
and renal cell carcinoma are expected to start later this year.
The research appears in the October 3, 1997 issue of Science.