eISSN: 1897-4309
ISSN: 1428-2526
Contemporary Oncology/Współczesna Onkologia
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vol. 14
Review paper

Immunotherapy of cancer and perspectives of its development

Jacek Mackiewicz
Andrzej Mackiewicz

Współczesna Onkologia (2010) vol.14; 2 (59-71)
Online publish date: 2010/04/30
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There is increasing evidence supporting the important role of the immune system in growth and progression of cancer. A better understanding of molecular and cellular mechanisms governing the immune system formed the basis for development of a number of innovative and promising cancer therapies modulating non-specific and specific anti-cancer immune responses. In the last 20 years the most impressive achievement in tumour immunotherapy has been the development of tech­nology for production of various specific monoclonal antibodies for human use and their approval for clinical practice. Interferon-alpha was the first approved cytokine for the treatment of cancer. Subsequently many clinical trials evaluating interleukin-2 led to its ap­proval for treatment of kidney cancer. Adoptive immunotherapy is a dynamically developing field of passive specific immunotherapy, where autologous tumour infiltrating or autologous peripheral blood lymphocytes are used. Non-specific immunostimulators and immunomodulators have not found wide approval in routine clinical practice; however, a suspension of heat-killed Mycobacterium vaccae seemed to be effective in a phase III study in the treatment of non-small cell lung cancer (adenocarcinoma), when compared to chemotherapy. In a number of clinical trials the efficacy of various types of so-called therapeutic cancer vaccines have been tested. They included peptide vaccines, viruses, DNA, heat-shock protein vaccine and cellular vaccines including genetically modified dendritic cells (DC) or tumour cells (GMTV). So far only in Canada and Russia have cancer vaccines been registered. A drug which is near FDA (Food & Drug Administration) approval in the USA, expected in May 2010, is Sipuleucel-T, which consists of autologous DC, incubated ex vivo with a fusion protein consisting of PAP (prostatic acid phosphate) conjugated with GM-CSF.
Bioimmunotherapeutics particularly designated for active specific cancer immunotherapy form a unique group of medicinal products of advanced technology. They display completely different pharmacodynamics and mode of action than chemotherapeutic agents or so-called small molecules in des­truction of cancer cells. However, regulatory authorities approve only methods adopted from clinical trials of chemical agents for assessment of the effectiveness of these drugs, including design of clinical trials, patient selection, end points and assessment of tumour clinical responses. Finally, similarly to other cancer treatment strategies, personalization of specific active immunotherapy with employment of new biomarkers is necessary. Currently there is intensive discussion regarding the needs of immunotherapy clinical trial design and execution modification. Without these changes we may overlook medicinal products which could bring a therapeutic benefit for patients.

immunotherapy, therapeutic cancer vaccines, monoclonal antibodies, adoptive immunotherapy, melanoma, renal cancer, prostate cancer

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