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Conrad Notes
a timely medical meeting newsletter
S.N. Khleif, MD, National Cancer Institute, Bethesda, Md, used custom-made mutated Ras vaccines to generate patient-tumor specific CD4+ and CD8+ T cells. A 15-patient study showed subcutaneously injected vaccines to be well tolerated and capable of generating an immune response. Some of these T cells from vaccinated patients killed corresponding cancer cells but not normal cells in laboratory tests.

Rationale Genetic alterations take place in cancer cells and lead to the synthesis of modified peptides not found in normal cells. Human colon, lung, and pancreatic cancers are commonly associated with mutations in Ras genes. If a patient's immune system could be made to recognize the specific altered peptide as foreign then this might stimulate an immune response (CD4+ and CD8+ T cells) to attack cancer cells while leaving healthy cells intact.
Procedure Step one involved determining the Ras genetic mutation in the patient's own tumor and making a specific vaccine to mimic the genetic mutation of the patient's tumor. Next, each patient received subcutaneously different concentrations of his/her vaccines containing the corresponding peptides.
Preliminary findings Good tolerance and a normal immune response followed vaccination of all 15 patients. Laboratory testing of biopsy samples from 8 of the 15 patients showed that 3 of 8 had the ability to recognize corresponding cancer cells that carry the genetic change, but not normal cells. Two of the three responders had colon cancer and the third, lung cancer.

The confirmed antigen-specific immune responses resulted from the three courses of vaccine given to these three patients. According to Khleif, the response consisted of a generated class II major histocompatibility complex (MHC) restricted to CD4+ and specific MHC class 1 human leukocyte antigen (HLA) A2 restricted to CD8+ cytotoxic T cells.

Future research Plans are underway to study higher doses of the vaccines and to use other adjuvants besides Detox to further stimulate the immune system.
Comments M.L. Rothenberg, MD, University of Texas Health Science Center, San Antonio, Tex, noted the use of the vaccine as a booster for the patient's immune system. The generated response may prevent clinical recurrence of the cancer or tumor progression.

Also, this report covers the vaccines' first use in humans and requires cautious interpretation. The same caveat holds for other reports on new experimental treatments as in the study of Swisher and Roth with adenoviral p53 therapy.

For professional correspondence, please contact Dr. Khleif at: khleif@nih.gov

Eugene A. Conrad

Presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 17-20, 1997
CONRAD NOTES, © 1997 All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078 / June 1997

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