Immunotherapy – Strategies for Expanding Its Role in the Treatment of All Major Tumor Sites

Abstract

Immunotherapy is widely regarded to have the ability to transform the treatment of cancer, with immune checkpoint inhibitors already in use for cancers such as advanced melanoma and non-small cell lung cancer (NSCLC). However, despite its potential, the widespread adoption of immunotherapy for the treatment of other cancers has been largely limited. This can be partly attributed to additional immunosuppressive mechanisms in the tumor microenvironment that help promote and maintain a state of T cell exhaustion. As such, the exploration of combinatory immunotherapies is an active area of research and includes the combination of immune checkpoint inhibitors with cytotoxic therapies, cancer vaccines and monoclonal antibodies against other co-inhibitory and co-stimulatory receptors. Strategies are also being employed to improve the homing, extravasation and survival of chimeric antigen receptor (CAR)-T cells in the tumor microenvironment. Furthermore, the development of immunotherapies targeted to one or multiple neoantigens unique to a specific tumor may act to enhance anti-tumor immunity, as well as reduce immune-related adverse events (irAEs). As immunotherapy evolves to become a mainstay treatment for cancer, it is imperative that optimum treatment regimens that maximize efficacy and limit toxicity are developed. Foremost, appropriate biomarkers must be identified to help tailor combinatory immunotherapies to the individual patient and hence pave the way to a new era of personalized medicine.

Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy

“…In adoptive cell transfer, tumor-reactive lymphocytes from the patient are collected, cultured ex vivo and reinfused, often along with growth factors, into the patient as therapy with the goal of recognizing, targeting, and destroying tumor cells. The cytotoxic T lymphocytes (CTLs) that can be used for this are tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR)-modified T-cells and chimeric antigen receptor (CAR)-modified T-cells [ 46 , 47 , 48 ]. In the latter, the cells are genetically engineered to target tumor-specific surface antigens.…”

“…However, despite the good results in hematological tumors, their application in solid tumors has been largely limited. This is believed to be due to difficulties in finding specific targetable antigens, T-cell homing, infiltration and survival in the TME [ 47 ]. Nevertheless, strategies are already being developed to overcome these obstacles, such as the split, universal, and programmable (SUPRA) CAR system, which uses universal receptors that allow target multiplexing and implements multiple advanced logic and control features [ 49 ].…”

“…The most widely used vaccines are peptide-based vaccines with immunogenic epitopes, usually from tumor-specific or tumor-associated antigens. This strategy typically uses synthetic peptides, DNA or RNA to encode the neoantigen; however, the fact that these neoantigens are not universal for a type of tumor or a group of patients limits their widespread use and leads to the development of tailored and even polyneoantigen vaccines [ 47 ].…”

Emerging Neuroblastoma 3D In Vitro Models for Pre-Clinical Assessments

“…PD1) and their ligand on tumor cells (e.g. PDL1), allowing the immune system to become able once again to kill cancer (84). The CAR-T/TCR consists of the patient's T-cells genetically modified to express unique tumor antigens that give them the ability to specifically target cancer cells, such as GD2 for neuroblastoma (84,85).…”

Initial Experience after Transition to Immune Checkpoint Inhibitors in Patients with Non-small Cell Lung Cancer Treated in a Rural Healthcare Region

“…The systemic treatment of advanced non-small cell lung cancer (NSCLC) has recently undergone significant transformations [1,2]. Platinum-based first-line chemotherapy and previous second-line regimens have been replaced by treatment with immune checkpoint inhibitors (ICI) such as pembrolizumab, atezolizumab, and nivolumab, both as monotherapy in first-or second-line treatments or in combination with chemotherapy in first-line treatment [3][4][5][6][7].…”