About this Research Topic

Background

Conventional cancer therapies, including surgery, radiotherapy and chemotherapy has shown positive effects in the treatment of patients with early-stage cancers, but they often fail to cure the majority of patients with cancers that develop metastasis in different organs. To overcome this issue more selective therapies have been developed in the last few decades, such as immunotherapy. The aim of immunotherapy is to enhance the power of immune system to target cancer, leading to a selective killing of cancer cells and a concomitant preservation of normal tissues. Several types of immunotherapy are used to treat cancer. These include: 1) Immune checkpoint inhibitors: block immune checkpoints, enhancing immune cell response against cancer cells 2) T-cell transfer therapy: boost anti-tumor activity of T-cells 3) Monoclonal antibodies: binds to specific tumor associated antigens on cancer cells so that they can be recognized and destroyed by the immune system 4) Cancer vaccines: elicit a strong and specific immune response against cancer cells 5) Immune system modulators: enhance immune system response against cancer cells.

Cancer cells use several strategies to resist the effect of immunotherapy, such as loss of MHC class I molecules, expression of neo-antigens, and over-expression of immunosuppressive molecules (IDO, PD-L1). Furthermore, cancer cells can secrete molecules that favour the accumulation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. These cells will release immunosuppressive cytokines, such as IL-10 and TGF-β, leading to the exhaustion of CTLs. MDSCs can also induce the generation of regulatory T cells, which suppress anti-tumor immune responses through the expression of inhibitory receptors and cytokines (TGF-β, IL-10, IDO, Tim-3 and LAG-3). To overcome tumor cells escaping from the immune pressure generated by immunotherapy, and to counteract the inhibitory activity of the tumor microenvironment on the immune system, next-generation immunotherapeutics have been generated or are under investigation and development. These include bispecific monoclonal antibodies, immunotoxins, fusion proteins, CAR-T cells, gene therapy and monoclonal antibodies with ADCC or CDC activity.

In this Research Topic, we are particularly interested in high-quality Original Research and Review articles that report the pre-clinical development of anti-tumor next-generation immunotherapeutics, such as bispecific monoclonal antibodies, immunotoxins, fusion proteins, CAR-T cells, gene therapy, cancer vaccines and monoclonal antibodies with ADCC or CDC activity. Manuscripts should focus on the impact of these new drugs in enhancing the immune system and overcoming the resistance of cancer cells to conventional immunotherapies. In addition to in vitro studies, manuscripts may also focus on the anti-tumoral activity of these drugs in vivo and report results from clinical trials. We are also interested in manuscripts reporting pre-clinical and clinical results derived from combination strategies between new drugs and conventional therapies.

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Massimo Fantini is an employee of Precision Biologics, Inc., a biotech company producing monoclonal antibodies for the treatment of solid tumors (Phase 1/2 clinical trials). Massimo Fantini holds a patent for one of these monoclonal antibodies.

Keywords: Monoclonal antibodies, Bispecific antibodies, CAR-T cells, Fusion proteins, Immunotoxins, Cancer vaccines, Gene therapy

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