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In most patients, melanoma in the skin creates an immune response against itself. This is seen in the partial regression of primary melanoma on the skin. In some instances the primary melanoma disappears completely from the skin, but not before melanoma cells spread from the skin to other sites in the body, such as regional lymph nodes. This is referred to as occult melanoma. Once melanoma has spread from the skin, natural responses by the immune system are less effective in controlling tumour growth. This may be because the immune response is less effective in particular parts of the body to which melanoma has spread or because the tumour cells undergo changes which make them less susceptible to the immune system. Over time, interaction between melanoma cells and the immune system also leads to change in immune responses that make them less effective in killing melanoma cells. These changes lead to the tumour becoming “immunologically silent” in patients. Various strategies are being tested to use immunotherapy against melanoma. Immunisation with melanoma vaccines aims to increase immune responses against the patient’s melanoma and to change the nature of the immune response to be more effective against melanoma. At present, the following programs are in progress:
Immunisation with Dendritic Cell Vaccines Dendritic cells (DCs) are responsible for presenting melanoma antigens to T cells in the immune system and for directing the nature of the response. It is believed that DCs in patients may not present antigen satisfactorily to the T cells but if isolated from the patient and activated in the laboratory with various agents they will be able to once more activate the immune response. Patients being treated with DC vaccines must have measurable tumors and be prepared to make regular visits to the SMU over a 16 week period. DCs are isolated from the patient’s blood and grown in the laboratory for 7 days. Melanoma antigen in the form of extracts from the patient’s tumor or from synthetic preparations are added to the DCs and injected into regional lymph nodes – usually those in the groin. Injections are at weekly intervals for the first 4 injections, one is given 2 weeks later, then 2 at 4 weekly intervals. Side effects have been minimal. Immunisation with Extracts of the Patient’s Melanoma It is considered that immunisation with vaccines prepared from a patient’s tumor, away from the site of the patient’s melanoma and mixed with helper antigens, may activate or increase responses against the patient’s tumor. One such vaccine was prepared from so-called heat shock proteins in the melanoma cell. This vaccine was prepared by a firm called “Antigenics” in the USA. Outcomes are being evaluated from the randomised trial comparing vaccine treatment with standard chemotherapy. Patients who have surgically removable tumor but who are not eligible for any trial may be offered treatment with vaccines prepared from their tumor on a compassionate basis. These treatments are not being evaluated in a trial setting and evidence of benefit is largely anecdotal. Immunisation with “Allogeneic” Vaccines or Synthetic Melanoma Antigens Many patients do not have melanoma available for preparation of vaccines from their tumor. In view of this, patients may be offered treatment with a standard vaccine prepared from a melanoma cell line that has been infected with vaccinia virus. The latter virus has been used to immunise people against smallpox, but in this setting is used to lyse the melanoma cells and to increase immune responses against the melanoma antigens. The vaccine (VMCL) has been evaluated in a randomised trial in Australia. It was associated with an approximate 10% increase in survival at 5 years and 20% at 10 years but the significance tests did not exclude that the results may have been due to chance. No significant side effects were associated with the treatment. Results were published in the Journal of Clinical Oncology, Volume 20, Pages 4181-4190, 2002.
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