New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness

Abstract

Antibodies have proven their high value in antitumor therapy over the last two decades. They are currently being used as the first-choice to treat some of the most frequent metastatic cancers, like HER2+ breast cancers or colorectal cancers, currently treated with trastuzumab (Herceptin) and bevacizumab (Avastin), respectively. The impressive therapeutic success of antibodies inhibiting immune checkpoints has extended the use of therapeutic antibodies to previously unanticipated tumor types. These anti-immune checkpoint antibodies allowed the cure of patients devoid of other therapeutic options, through the recovery of the patient’s own immune response against the tumor. In this review, we describe how the antibody-based therapies will evolve, including the use of antibodies in combinations, their main characteristics, advantages, and how they could contribute to significantly increase the chances of success in cancer therapy. Indeed, novel combinations will consist of mixtures of antibodies against either different epitopes of the same molecule or different targets on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding tumor cells, immune cells or extracellular molecules; immunomodulatory antibodies; antibody-based molecules, including fusion proteins between a ligand or a receptor domain and the IgG Fab or Fc fragments; autologous or heterologous cells; and different formats of vaccines. Through complementary mechanisms of action, these combinations could contribute to elude the current limitations of a single antibody which recognizes only one particular epitope. These combinations may allow the simultaneous attack of the cancer cells by using the help of the own immune cells and exerting wider therapeutic effects, based on a more specific, fast, and robust response, trying to mimic the action of the immune system.

GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

“…The approach described here – studies of patient-derived cells and cell lines to define a GPCR profile and the differential expression of GPCRs of cancer cells compared to that of normal cell precursors—should be applicable to other types of cancer. Perhaps therapies directed at such GPCRs can be part of therapeutic cocktails with multiple agents, especially since drug combinations may be able to optimize efficacy and minimize side-effects and drug resistance in cancer therapy ( Atkins and Larkin, 2016 ; Alsaab et al, 2017 ; Corraliza-Gorjón et al, 2017 ; Gotwals et al, 2017 ; Lopez and Banerji, 2017 ).…”

Immunotherapy-based combination strategies for treatment of gastrointestinal cancers: current status and future prospects

“…Anti-ERBB family antibodies comprise another important type of targeted agents, which have been widely used in clinical practices for GI cancer. Aside from directly inhibiting important signal pathways, which control proliferation, anti-apoptosis, and invasion of tumor cells, recombinant antibodies can also induce host anti-tumor immune response through antibody-dependent cell-cytotoxicity (ADCC), antibody-dependent cell-phagocytosis and complement-dependent cytotoxicity [61]. The identification of the immunoglobulin G1 (IgG1) backbone of antibodies, such as cetuximab and trastuzumab, is necessary to mobilize immune responses [62].…”

Will a mAb-Based Immunotherapy Directed against Cancer Stem Cells Be Feasible?

“…It should be noted that these experiments were carried out in xenotransplants, where the only cells expressing CD44, CD123, CD47, or TIM-3 were the transplanted tumor cells, thus any putative toxic effects on other body cells expressing these markers CD44 + , CD123 + , CD47 + , or TIM-3 + could not be assessed in these models. However, a possibility, discussed in details in another review from this issue is to use combinations of antibodies ( 8 ), where even if the antibodies mentioned earlier for the treatment of AML used separately could be also toxic for the normal tissues, their combination (CD44, CD123, CD47, and TIM-3) could use smaller doses of each one of them, avoiding the concentrations required to induce toxicity in normal cells, but still be effective killing the CSC on AML. This is one of the possibilities that should be investigated for the treatment of AML and other types of cancer.…”

“…Indeed, they are able to redirect the antitumor immune response and allow envisaging the possibility of a cure for cancer patients. Obviously, the cure for cancer patients might come from the use of more or less complex combinations of antibodies that will include other drugs or cells ( 8 ).…”