Cancer treatment: the combination of vaccination with other therapies

Abstract

Harnessing of the immune system by the development of 'therapeutic' vaccines, for the battle against cancer has been the focus of tremendous research eVorts over the past two decades. As an illustration of the impressive amounts of data gathered over the past years, numerous antigens expressed on the surface of cancer cells, have been characterized. To this end, recent years research has focussed on characterization of antigens that play an important role for the growth and survival of cancer cells. Antiapoptotic molecules like survivin that enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies represent prime vaccination candidates. The characterization of a high number of tumor antigens allow the concurrent or serial immunological targeting of diVerent proteins associated with such cancer traits. Moreover, while vaccination in itself is a promising new approach to Wght cancer, the combination with additional therapy could create a number of synergistic eVects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending on the speciWc chemotherapeutics. Also, chemotherapy represents one of several options available for clearance of CD4 + Foxp3 + regulatory T cells. Moreover, therapies based on monoclonal antibodies may have synergistic potential in combination with vaccination, both when used for targeting of tumor cells and endothelial cells. The eYcacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology of the cancer cell per se, but also considering how treatment may inXuence the malignant cell population as well as the immune system.

CD8 T-cell Responses against Cyclin B1 in Breast Cancer Patients with Tumors Overexpressing p53

“…These tumor-specific alterations, playing an important role for the malignant properties of the cancer cell, also offer targets for therapeutic intervention, for example, antisense therapy, small molecule inhibitors, and immunotherapy (22). To the latter, several groups of proteins sharing the functional property of being important for tumor cell growth and/or survival are recognized by host T cells.…”

“…Moreover, mutated p53 is associated with bad prognosis, for example, by poor response to chemotherapy, which implies that targeting of cyclin B1 could synergistically be combined with conventional chemotherapy (22). Importantly, although p53 seems to be an obvious target and induced immune responses seem to be clinically relevant (15), it seems that targeting of cyclin B1 is more broadly applicable because cyclin B1 is overexpressed also when tumor cells are devoid of p53 protein.…”

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab

“…1,2 Perhaps the best example of such an agent is lenalidomide (LEN), [3][4][5] a structural analog of thalidomide with similar but more potent immunomodulatory activities. [6][7][8] Since its approval by the FDA, lenalidomide has demonstrated impressive results in patients with newly-diagnosed and relapsed multiple myeloma 9,10 and also improved graft versus multiple myeloma effects after allogeneic stem cell transplantation.…”

Immunotherapy of cancer and perspectives of its development

“…Badania przedkliniczne oraz wczesne badania kliniczne wskazują na potencjał kojarzenia aktywnej immunoterapii z innymi metodami leczenia, uważanymi zarówno za konwencjonalne, jak i wciąż doświadczalne [118,119]. Niektóre chemioterapeutyki, którym dotychczas przypisywano wyłącznie efekt immunosupresyjny dzięki hamowaniu proliferacji dzielących się komórek immunologicznych w szpiku kostnym oraz obwodowych tkankach limfatycznych, wykazują działania immunomodulujące czy wręcz immunostymulujące na drodze wielu różnych mechanizmów.…”