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Cancer vaccine induces integrated immune response, novel monitoring shows

Karla Gale

Reuters Health

Posting Date: February 20, 2004

Last Updated: 2004-02-20 12:13:21 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Using a new technique to monitor antibody levels as well as CD8+ T cells and CD4+ T cells, researchers in New York have demonstrated that a therapeutic cancer vaccine elicits a fully integrated immune response in patients with non-small-cell lung cancer.

Their research is published in the March 1st issue of the Journal of Immunology.

"The Cancer Vaccine Collaborative hopes to standardize approaches to evaluating immune responses," senior author Dr. Sacha Gnjatic told Reuters Health. By focusing on the strength of the immune response, "we will be able to proceed more quickly into vaccine development of new antigenic constructs."

This approach contrasts to many vaccine trials currently underway, he added, "which have looked primarily at clinical effects without focusing necessarily on immune response to particular antigens."

Dr. Gnjatic, at the Ludwig Institute for Cancer Research at Memorial Sloan-Kettering Cancer Center, and other members of the Cancer Vaccine Collaborative conducted a phase I trial of a vaccine containing MAGE-3 protein, which is expressed in testicular germ cells and many tumors, but not in normal tissue.

Following surgical resection of non-small-cell lung tumors, 19 patients underwent immunization with MAGE-3, four times at 3-week intervals. Eight were treated with MAGE-3 in combination with an adjuvant. Immune responses tended to be stronger in those treated with adjuvant.

In the latter group, seven showed a marked increase in serum concentrations of anti-MAGE-3, reaching maximum levels at day 85, the end of the observation period. Four achieved marked increases in CD4+ T cell responses against a MAGE-3 epitope, producing Th1 type cytokines but not Th2 type. Peptide-specific CD8+ T cell responses were observed in two patients.

According to Dr. Gnjatic, activating all three components of the immune response "in our opinion would make an effective vaccine." He explained that activated CD4+ T cells are important for initiating, amplifying, and maintaining CD8+ T cell responses.

The challenge up until now has been measuring peptide-specific CD4+ responses against normally high background levels. They overcame this obstacle by using a modified ELISPOT assay based on cytokine secretion.

"The data presented in this work lay the grounds for the design of vaccine constructs and immunization protocols to define conditions for maximal immunogenicity," the authors conclude. The end result will be to "answer the most important question in tumor immunology: can immunization affect the course of human cancer?"

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