Combination of active specific immunotherapy or adoptive antibody or lymphocyte immunotherapy with chemotherapy in the treatment of cancer

Abstract

Successful treatment of cancer patients with a combination of monoclonal antibodies (mAb) and chemotherapeutic drugs has spawned various other forms of additional combination therapies, including vaccines or adoptive lymphocyte transfer combined with chemotherapeutics. These therapies were effective against established tumors in animal models and showed promising results in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. Although combination between immunotherapy and chemotherapy has long been viewed as incompatible as chemotherapy, especially in high doses meant to increase anti-tumor efficacy, has induced immunosuppression, various mechanisms may explain the reported synergistic effects of the two types of therapies. Thus direct effects of chemotherapy on tumor or host environment, such as induction of tumor cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for enhancement of immunotherapy by chemotherapy. Furthermore, induction of lymphopenia by chemotherapy has increased the efficacy of adoptive lymphocyte transfer in cancer patients. On the other hand, immunotherapy may directly modulate the tumor's sensitivity to chemotherapy. Thus, anti-tumor mAb can increase the sensitivity of tumor cells to chemotherapeutic drugs and patients treated first with immunotherapy followed by chemotherapy showed higher clinical response rates than patients that had received chemotherapy alone. In conclusion, combination of active specific immunotherapy or adoptive mAb or lymphocyte immunotherapy with chemotherapy has great potential for the treatment of cancer patients which needs to be confirmed in larger controlled and randomized Phase III trials.

Paclitaxel enhances early dendritic cell maturation and function through TLR4 signaling in mice

“…[1; 2] Most pre-clinical studies suggest that vaccines work best in minimal residual disease, which has led to the exploration of combining vaccines with standard cancer treatments such as chemotherapy and radiation, since these modalities can often reduce overall tumor burden or activate the immune system. [3; 4; 5; 6; 7; 8] Standard treatment doses of chemotherapy, however, are often detrimental to the effectiveness of tumor vaccines, most likely due to their cytotoxic effects on activated T cells. Therefore, subclinical doses of standard chemotherapeutic agents have been tested in both animal models and clinical trials for their ability to synergistically enhance the immune activity of vaccines.…”

Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic

“…Tumor-rejection antigens have been identified for a variety of human malignancies [2], and circulating CD8 + cytotoxic T lymphocytes (CTL) able to recognize peptides derived from these antigens are detectable in the blood of patients with cancer [3–5]. The induction and expansion of tumor-specific CTL is a major goal of currently available cancer vaccines [6]. However, the effectiveness of CTL generated by anti-tumor vaccines in cancer patients is often compromised by tumor escape mechanisms, including death of tumor-antigen-specific effector T cells [7, 8].…”

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect

“…Among the standard therapies, chemotherapy is still the first-line treatment for many malignancies. In the past, the observed negative effect of many chemotherapeutics on lymphocytes [32][33][34] raised doubts about the suitability of chemotherapy for combination with immunotherapy. However, recent clinical research addressing this point demonstrates that a group of chemotherapeutics can induce immunogenic cell death and act synergistically with immunotherapy [35][36][37].…”