Contact:
Lisa Jacobs
Michael Fagan
212/880-5300
Annual Meeting News Room:
303/446-4472
EMBARGOED FOR RELEASE UNTIL TIME OF EACH PRESENTATION: (See times indicated below)
BEYOND CHEMOTHERAPY
-- Novel Approaches To Treatment Show Promise For Next Generation Of Targeted Cancer Therapies --
-- Press Briefing Tuesday, May 20, 10:00 AM (MDT) --
Denver, CO -- May 20, 1997 -- With a growing number of gene mutations strongly correlated with cancer, and new clues about stimulating the bodyÃs immune system, clinical research is increasingly focusing on targeting the source of cancerous growth -- mutated genes and poorly functioning immune systems.
While traditional chemotherapy can be effective in killing cancer cells, it also attacks healthy cells, resulting in unwanted, damaging side effects. New therapies discussed today at a press conference entitled ìBeyond Chemotherapyî at the Thirty-third Annual Meeting of the American Society of Clinical Oncology, take a variety of approaches in recognizing and attacking genetic mutations in cancerous cells, while leaving healthy cells intact.
ìAs we gain greater insight into the basic processes responsible for turning a normal cell into a cancer cell, we are identifying new weapons and new targets for the treatment and prevention of cancer,î said Mace L. Rothenberg, MD, of University of Texas Health Science Center, the moderator of the press conference. ìThis work is important because it shows that these new approaches can be used safely in people, and have a distinct and measurable impact on the cancer cells and the host. At the present time, however, we canÃt tell how effective these new therapies are in the treatment or prevention of cancer. That will require evaluation of a much larger number of patients in carefully conducted clinical trials.î
These approaches -- including tumor ìvaccinesî to enhance immune response, antisense therapy to block the production of damaging proteins, and the use of a cold virus to infiltrate and kill genetically-damaged cancer cells -- are in the early stages of clinical trials, but all promise to make significant contributions to the next generation of cancer treatments.
Skin Cancer Vaccine Trial Shows Safety, Immune Response and Anti-Tumor Activity
R. Soiffer, MD, et al, Dana-Farber Cancer Institute, ìInduction of Anti-Tumor Immunity by Autologous Melanoma Vaccines Genetically Engineered to Secrete Granulocyte-Macrophage Colony Stimulating Factorî (Integrated Session, Monday May 19, 8:00 a.m., [MDT] Ballroom 4, Abstract #1759)
Gene transfer technologies are now being explored in patients with metastatic melanoma to study new uses of granulocyte macrophage colony stimulating factor (GM-CSF), a substance long used in bone marrow transplants to stimulate white blood cell growth. In a new study conducted by researchers at the Dana-Farber Cancer Institute and Massachusetts General Hospital, tumor cells engineered to secrete GM-CSF show promise in creating an immune response to attack cancerous cells in patients with melanoma.
The phase I study of 32 patients, conducted by Robert Soiffer, MD, Thomas Lynch, MD and Glenn Dranoff, MD of Dana-Farber and Massachusetts General and sponsored by Somatix Therapy Corporation, tested the safety of injecting skin cancer patients with melanoma cells engineered to secrete GM-CSF.
The clinical trial demonstrated that the tumor vaccine is safe and well-tolerated, and that it produced long-lasting, specific anti-tumor immunity at distant sites where the cancer had metastasized. These responses have produced partial tumor destruction in a number of the evaluable patients. The nature of these immune responses are being further defined so that future efforts can be directed at stimulating these reactions. This type of immune therapy, although initiated in patients with melanoma, will also soon be explored in patients with other malignancies such as lung cancer.
New Therapy Introduces Manufactured Genetic Mutations to Stimulate the Immune System
S.N. Khleif, MD, et al, National Cancer Institute, ìThe Generation of CD4+ and CD8+ T- Cell Responses From Patients Vaccinated with Mutant RAS Peptides Corresponding to the PatientÃs Own RAS Mutationî (Oral Session, Tuesday, May 20, 3:45 p.m. [MDT], Room C108-112, Abstract #1566)
Mutations of oncogenes (cancer genes), such as Ras and p53, are some of the most common genetic alterations that lead to cancerous growth. A novel approach to attacking this unique characteristic of cancer takes advantage of the bodyÃs own defenses by introducing a foreign piece of protein that mimics the harmful cellÃs mutation, teaching the immune system to recognize and attack the cancerous cells while leaving healthy cells intact.
Researchers led by Samir N. Khleif, MD at the National Cancer Institute manufactured and vaccinated patients with the piece of the changed Ras protein that corresponded to the bodyÃs own tumor. Taking a similar approach to vaccines in common use to prevent certain infectious diseases, this trial was designed to test whether the foreign Ras proteins are recognized as invaders, thus stimulating an immune response.
Initial results indicate that the researchers were successful at generating an immune response -- i.e., the generation of specific immune cells (CD4+ and, for the first time, CD8+ T cells) -- to the mutated Ras proteins in 3 of the 8 patients, but not the normal (not mutated) Ras gene, which is carried by the normal cells. The study also indicated that the treatment is well tolerated, with no evidence of serious side effects.
First Clinical Results from Use of Cold Virus to Attack Common Genetic Cause of Cancer
D. Von Hoff, et al, Institute for Drug Development, Cancer Therapy and Research Center, and University of Texas Health Science Center, ìPhase I trial of Intratumoral Injection with an E1B-Attenuated Adenovirus, Onyx-015 in Patients with Recurrent p53 (-) Head and Neck Cancerî (Oral Session, Monday May 19, 8:00 a.m. [MDT], Room C108-112, Abstract #1362)
S. Swisher, et al, University of Texas M.D. Anderson Cancer Center, ìAdenoviral Mediated p53 Gene Transfer in Patients with Advanced Non-Small Cell Lung Cancerî (Oral Session, Tuesday May 20, 3:30 p.m. [MDT], Room C108-112, Abstract #1565)
In two closely watched studies that could have implications for up to half of all cancer cases, researchers presented results from two phase I trials using a mutated cold virus to infect and destroy cancerous cells.
The missing or mutated p53 gene has been linked to approximately half of all cancer cases. Under normal circumstances, this gene regulates apoptosis, or the natural process of cell death; when missing or mutated, cells are allowed to divide unchecked, leading to cancer.
In a study conducted by Daniel Von Hoff, MD of the Cancer Therapy and Research Center and University of Texas Health Science Center in San Antonio, and colleagues at the Beatson Oncology Center in Glasgow, Scotland and the Physician Reliance Network in Dallas, TX, researchers engineered and injected a mutated cold virus designed to infect and kill only cells with the p53 mutation, not healthy cells, thus directly attacking the source of cancerous growth. Patients with head and neck tumors were injected with the mutated cold virus, E1B-attenuated adenovirus. In encouraging results, some of the patients had evidence of some tumor cell death at the site of the injections, and additional patients showed improvement of tumor-associated symptoms.
In a separate study, Stephen Swisher, MD and Jack Roth, MD of the M.D. Anderson Cancer Center evaluated the effect of monthly injections of a recombinant adenovirus carrying the normal p53 gene alone or in combination with cisplatinum chemotherapy in 21 patients with advanced non-small cell lung cancer, in whom all previous treatments had failed. The strategy was designed to ìpiggybackî a normal p53 gene on the engineered virus into cancerous cells, thus re-enabling the cellÃs ability to die off, killing the tumor cells. The results showed that the normal p53 gene could be transferred and expressed in the tumors by the recombinant adenovirus with minimal side-effects. Promising anti-tumor activity was observed with higher doses of Adp53 and when Adp53 was combined with the standard chemotherapy drug cisplatinum.
New Antisense Therapy Shows Progress in Blocking of Proteins Linked with Cancer
B. Sikic, MD, Stanford University School of Medicine, Oncology Division, ìA Phase I Trial of an Antisense Oligonucleotide Targeted to Protein Kinase C-alpha Delivered by 21 Day Continuous Intravenous Infusionî with A.R. Yuen, J. Halsey, G.A. Fisher, J.P. Pribble, R.M. Smith and A. Dorr. (Poster Session, Monday, May 19, 8:00 a.m. [MDT], Currigan A, Abstract #741)
A new treatment approach called ìantisenseî therapy shows promise in inhibiting the production of proteins associated with the growth of various types of cancer. Antisense therapy introduces strands of manufactured DNA (antisense) designed to bind to and inactivate strands of messenger RNA (sense) that produce proteins linked with cancer.
It is thought that the protein kinase C-alpha may play a role in the development and maintenance of several tumor types. In the first trial to test this particular approach, antisense research conducted by a group headed by Branimir I. Sikic, MD of the Stanford University School of Medicine, Oncology Division, found that intravenous transfusions of antisense DNA designed to block kinase production were well-tolerated among seventeen patients with cancers of the pancreas, colon, stomach, lung, breast, ovary, and sarcomas. Higher doses were associated with toxicity consisting of decreased platelet counts and fatigue in some patients.
The study also found that one patient with ovarian cancer has had a partial remission of her disease for at least nine months, and two other patients with ovarian cancer have had a decrease in their serum tumor marker. The antisense DNA drug is manufactured and the study is supported by Isis Pharmaceuticals Corporation in collaboration with Novartis Pharmaceutical Corporation.
# # # #
RSS