Abstract
With the advent of cancer immunotherapy, there has been a major improvement in patient’s quality of life and survival. The growth of cancer immunotherapy has dramatically changed our understanding of the basics of cancer biology and has altered the standards of care (surgery, radiotherapy, and chemotherapy) for patients. Cancer immunotherapy has generated significant excitement with the success of chimeric antigen receptor (CAR) T cell therapy in particular. Clinical results using CAR-T for hematological malignancies have led to the approval of four CD19-targeted and one B-cell maturation antigen (BCMA)-targeted cell therapy products by the US Food and Drug Administration (FDA). Also, immune checkpoint inhibitors such as antibodies against Programmed Cell Death-1 (PD-1), Programmed Cell Death Ligand-1 (PD-L1), and Cytotoxic T-Lymphocyte-Associated Antigen 4 (CTLA-4) have shown promising therapeutic outcomes and long-lasting clinical effect in several tumor types and patients who are refractory to other treatments. Despite these promising results, the success of cancer immunotherapy in solid tumors has been limited due to several barriers, which include immunosuppressive tumor microenvironment (TME), inefficient trafficking, and heterogeneity of tumor antigens. This is further compounded by the high intra-tumoral pressure of solid tumors, which presents an additional challenge to successfully delivering treatments to solid tumors. In this review, we will outline and propose specific approaches that may overcome these immunological and physical barriers to improve the outcomes in solid tumor patients receiving immunotherapies.
Highlights
Cancer immunotherapy dates back to William B
Constant exposure to a tumor antigen leads to the enhanced expression of inhibitory receptors such as Programmed Cell Death-1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T-cell immunoglobulin domain and mucin domain protein-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), and band T lymphocyte attenuator (BTLA) [40,41]
Immunotherapy has shown great promise in certain indications, immune checkpoint inhibitors (ICI) and cell therapy have far failed to make a major impact on certain solid tumor indications
Summary
Cancer immunotherapy dates back to William B. Coley in 1891 when he began treating cancer patients with different combinations of bacteria and their derivatives to provoke an immune response [1]. While the immune system was not understood or recognized at that time, Coley and others observed that patient responses to infection were on occasion associated with tumor regression. Current types of immunotherapy that have been explored include monoclonal antibodies (mAb), immune checkpoint inhibitors (ICI), oncolytic viral platforms (OV), cancer vaccines, adoptive cell therapy (ACT), and various combinatorial approaches [3]. We will focus on the current standards of care in Biomedicines 2022, 10, 655. Biomedicines 2022, 10, 655 cancer immunotherapy, with a strong focus on the promise and limitations of ACT [4], which includes tumor-infiltrating lymphocytes (TIL’s), CAR-T cells, and CAR-natural killer cells (CAR-NK)
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