Cancer Vaccines

Producing a vaccine against cancer has been a dream since the earliest days of immunology. The goal of a cancer vaccine, however, is different than for an infectious disease vaccine. The number of different types of cancer is huge—as we said at the beginning, as many as there are different types of cells in the body. So undertaking mass vaccination programs prophylactically—before disease develops—is not going to be practical. Rather, we will want to develop individually tailored vaccines that can reverse the disease once it has become clinically detectable.

It is only in recent years that we have understood both vaccination and cancer well enough to make informed attempts at producing a cancer vaccine. Early attempts often involved something as simple as surgically removing a patient's tumor, grinding it up, irradiating it, and reimplanting it into the body along with adjuvants known to stimulate antibody responses in general. Occasional positive effects were seen, but they were not consistent and this approach was soon abandoned.

But now we realize that, as with vaccines for intracellular parasites, we need a vaccine that will selectively stimulate production of CD8 T cells, and for that we need to know which peptides associated with the cancer are most likely to produce an effective CD8 response. This approach has been tested in mice and has given impressive results.

In humans, a lot of work has been done to find out which pep-tides would be best to use for a variety of common tumor vaccines. The most impressive results have been obtained with malignant melanoma (Figure 11.1), and clinical trials with vaccines for this cancer have been under way for the past several years. Melanoma is one of the most difficult cancers to treat, particularly if it has spread beyond the original site. Once a tumor has spread, or become metastatic, only systemic treatments such as chemotherapy, and possibly a vaccine, can be effective.

Typical of the antigens defined for melanoma are MART-1 and

figure 11.1

Malignant melanoma lesion.

gp 100. Both of these are nonmutated proteins normally found at low levels in skin pigmentation cells (melanocytes) but overproduced in melanocytes that have become cancerous. The genes for MART-1 and gp 100 have been cloned, and corresponding peptides have been identified that would make the best vaccines. Clinical trials using a gp 100 peptide, administered together with stimulatory cytokines, yielded tumor regressions in 42% of patients with advanced melanoma. In a second trial a selected peptide from MART-1 was shown to induce significant CD8 responses in melanoma patients, which correlated with a prolonged time to relapse. The melanoma trials have now advanced to include patients with less advanced disease, where the results can be expected to be even better.

Vaccine trials with peptides from other cancers including breast, cervical, and pancreatic are under way and have given broadly similar results where reported. As with the melanoma trials, these trials are in the early stages and are restricted to patients with advanced cancer who have failed conventional treatments. However, it must be admitted that at present, although CD8 responses have been good, tumor regressions have not been as impressive as with melanoma. But the melanoma studies have been going on much longer. Everyone expects that as we learn more about exactly which peptides produce the best CD8 responses in these other cancers, the success rate will improve.

So will DNA vaccination replace any of the current standard treatments for cancer patients? Certainly not in the immediate future. The first line of standard cancer treatment, where possible, is simple physical reduction of the tumor mass by surgery. In some cases that is a complete cure in itself. But for the majority of cases, where the tumor is inaccessible to surgery or where surgery reduces but does not completely eliminate the tumor load, follow-up treatment with other modalities is required. Radiation therapy can be used to clean up residual tumor at the primary tumor site. Chemotherapy can be used for the same purpose, and can also chase down and (hopefully) eliminate metastases that have spread beyond the primary site.

No vaccine, however effective, would likely displace surgery for accessible tumors. Reducing the tumor burden will make the job of any vaccine that much simpler. And to the extent that radiation or chemotherapy can reduce the tumor load further, the immunotherapist is just that much further ahead. Certainly, if a particular vaccine turns out to be particularly effective, it is possible that radiation therapy or chemotherapy could be reduced, or even possibly eliminated, given the serious side effects that come with these treatments. Given the recent successes of cancer vaccines and the tremendous opportunities that lie ahead for this new modality, it would be surprising indeed if we did not see it moving into the clinic, as part of the oncologist's bag of standard anticancer weapons, by the end of this decade.

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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