Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new member of the coronavirus family that can cause coronavirus disease 2019 (COVID‐19). COVID‐9 has become a global pandemic with severe health issues around the world. Identifying the accurate immunopathogenesis of the COVID‐19 and the immune response against SARS‐CoV‐2 is necessary for the development of therapeutic approaches and rational drug design. This paper aims to overview the updated clinical data on the immunopathogenesis of the COVID‐19 and review the innate and adaptive immune response to SARS‐CoV‐2. Also, challenges of the immune response to SARS‐CoV‐2 leading to dysfunctional immune response and their contribution to the progression of the disease have been discussed. To achieve a more efficient immune response, multiple methods could be applied, including regulation of the immune response, augmentation of the immune system against the virus, inhibition of the dysfunctional immune checkpoints, and inhibition of the viral replication/infection. Based on the immune response against SARS‐CoV‐2 and its dysfunction, we introduce potential immunotherapies as well as reviewing recruiting/completed clinical trials of COVID‐19.

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T cells equipped with chimeric antigen receptors (CAR T cells) have recently provided promising advances as a novel immunotherapeutic approach for cancer treatment. CAR T cell therapy has shown stunning results especially in B-cell malignancies; however, it has shown less success against solid tumors, which is more supposed to be related to the specific characteristics of the tumor microenvironment. In this review, we discuss the structure of the CAR, current clinical advantages from finished and ongoing trials, adverse effects, challenges and controversies, new engineering methods of CAR, and clinical considerations that are associated with CAR T cell therapy both in hematological malignancies and solid tumors. Also, we provide a comprehensive description of recently introduced modifications for designing smarter models of CAR T cells. Specific hurdles and problems that limit the optimal function of CAR T cells, especially on solid tumors, and possible solutions according to new modifications and generations of CAR T cells have been introduced here. We also provide information of the future directions on how to enhance engineering the next smarter generations of CAR T cells in order to decrease the adverse effects and increase the potency and efficacy of CAR T cells against cancer.

Graphical abstract

Graphical abstract Natural Killer (NK) cells are critical members of the innate immunity lymphocytes and have a critical role in host defense against malignant cells. Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR) redirects the specificity of the immune cell against a target-specific antigen. ACT has recently created an outstanding opportunity for cancer treatment. Unlike CAR-armored T cells which hadnsome shortcomings as the CAR-receiving construct, Major histocompatibility complex (MHC)-independency, shorter lifespan, the potential to produce an off-the-shelf immune product, and potent anti-tumor properties of the NK cells has introduced NK cells as a potent alternative target for expression of CAR. Here, we aim to provide an updated overview on the current improvements in CAR NK design and immunobiology and describe the potential of CAR-modified NK cells as an alternative “off-the-shelf” carrier of CAR. We also provide lists for the sources of NK cells in the process of CAR NK cell production, different methods for transduction of the CAR genetic sequence to NK cells, the differences between CAR T and CAR NK, and CAR NK-targeted tumor antigens in current studies. Additionally, we provide data on recently published preclinical and clinical studies of CAR NK therapy and a list of finished and ongoing clinical trials. For achieving CAR NK products with higher efficacy and safety, we discuss current challenges in transduction and expansion of CAR NK cells, CAR NK therapy side effects, and challenges that limit the optimal efficacy of CAR NK cells and recommend possible solutions to enhance the persistence, function, safety, and efficacy of CAR NK cells with a special focus on solid tumors.