Combination of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience

Abstract

In vitro studies have demonstrated that cancer-specific T cell cytotoxicity can be induced both ex vivo and in vivo, but this therapeutic strategy should probably be used as an integrated part of a cancer treatment regimen. Initial chemotherapy should be administered to reduce the cancer cell burden and disease-induced immune defects. This could be followed by autologous stem cell transplantation that is a safe procedure including both high-dose disease-directed chemotherapy and the possibility for ex vivo enrichment of the immunocompetent graft cells. The most intensive conventional chemotherapy and stem cell transplantation are used especially in the treatment of aggressive hematologic malignancies; both strategies induce T cell defects that may last for several months but cancer-specific T cell reactivity is maintained after both procedures. Enhancement of anticancer T cell cytotoxicity is possible but posttransplant vaccination therapy should probably be combined with optimalisation of immunoregulatory networks. Such combinatory regimens should be suitable for patients with aggressive hematological malignancies and probably also for other cancer patients.

Immunogenic apoptosis in human acute myeloid leukemia (AML): primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis

“…Furthermore, the levels of circulating AMl-recognizing t cells can increase after chemotherapy (17). Induction of immunogenic apoptosis with calreticulin exposure and Hsp release by the AMl cells may then be important, and in the present study we describe that dying primary human AMl cells can expose calreticulin and release Hsp70 and Hsp90.…”

“…previous studies have then focused on induction of apoptosis in the AMl cells, whereas the apoptotic phenotype has not been characterized in detail even though antileukemic immune reactivity has a documented clinical effect for these patients especially after allogeneic stem cell transplantation (17). to the best of our knowledge only one study has examined immunogenic characteristics in primary human AMl cells; this was a small study including only 4 patients and the results suggest that calreticulin can be exposed by AMl cells for certain patients (18).…”

A model for effects of adaptive immunity on tumor response to chemotherapy and chemoimmunotherapy

“…Indeed, even high-dose chemotherapy has been combined with immunotherapy for hematological malignancies, as reviewed by Liseth et al [63].…”

Engineered Drug Resistant Cell-Mediated Immunotherapy

“…For example, these agents can be detrimental to the establishment of robust anti-tumor immunocompetent cells due to the non-specific cellular toxicity of many anti-cancer agents. Intensive chemotherapy frequently administered to treat patients with advanced cancer can result in lymphopenia, which decrease the numbers and function of potential anti-cancer T cells in the blood thereby blunting the anti-tumor immune responses (Liseth et al, 2010). Tumor drug resistance can also develop, resulting in ineffective chemotherapy treatment 337 Engineered Drug Resistant Cell-Mediated Immunotherapy (Michael & Doherty, 2005).…”