Immunotherapy-Associated Cardiotoxicity of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T Cell Therapy: Diagnostic and Management Challenges and Strategies

Gynecological tumors are malignancies with both high morbidity and mortality. To date, only a few chemotherapeutic agents have shown efficacy against these cancer types (only ovarian cancer responds to several agents, especially platinum-based combinations). Within this context, the discovery of immune checkpoint inhibitors has led to numerous clinical studies being carried out that have also demonstrated their activity in these cancer types. More recently, following the development of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, this strategy was also tested in solid tumors, including gynecological cancers. In this article, we focus on the molecular basis of gynecological tumors that makes them potential candidates for immunotherapy. We also provide an overview of the main immunotherapy studies divided by tumor type and report on CAR technology and the studies currently underway in the area of gynecological malignancies.

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Immunotherapy use in kidney transplant recipients: Immune checkpoint inhibitors and CAR-T cell therapy

Journal of Onco-Nephrology ◽

10.1177/2399369320953163 ◽

2020 ◽

Vol 4 (3) ◽

pp. 165-170

Author(s):

Claude Bassil ◽

Farhad Khimani

Keyword(s):

T Cell ◽

Renal Transplant ◽

Acute Rejection ◽

Cell Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Transplant Recipients ◽

T Cell Therapy ◽

Car T

Cancer immunotherapy including the use of immune checkpoint inhibitors (ICI) and chimeric antigen receptor T cell therapy (CAR-T) are showing a promising role as part of cancer therapy and slowly replacing conventional chemotherapy. However, the use of ICI and CAR-T in organ transplant recipients with malignancies could be complicated with acute rejection and graft loss. Many proposed immunosuppressive (IS) regimens showed a probable role in preventing acute rejection related to ICI, including the use of a single ICI rather than double ICI, concomitant use of glucocorticoids (GC), converting tacrolimus to mTor inhibitors (m-TorI) and avoid close sequencing of ICI agents. Furthermore, low dose prednisone (LDP) before CAR-T infusion in patients with stable allograft kidney function could favor the regulatory T cells (T-regs), actively regulating alloimmune responses, and maintaining self-tolerance of the renal transplant. Further prospective trials will be needed to examine the long-term effect of these regimens in renal transplant recipients undergoing CAR-T or receiving ICI as curative therapies for their refractory cancers.

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Current Challenges and Strategies for Chimeric Antigen Receptor-T Cell Therapy in Solid Tumors

Critical Reviews in Immunology ◽

10.1615/critrevimmunol.2020036178 ◽

2020 ◽

Author(s):

Junfei Chen ◽

Hua Jiang

Keyword(s):

T Cell ◽

Cell Therapy ◽

Solid Tumors ◽

Chimeric Antigen Receptor ◽

Antigen Receptor ◽

T Cell Therapy ◽

Challenges And Strategies

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Immunotherapy in patients with cervical cancer

Tumors of female reproductive system ◽

10.17650/1994-4098-2020-16-2-72-77 ◽

2020 ◽

Vol 16 (2) ◽

pp. 72-77

Author(s):

A. G. Kedrova

Keyword(s):

Cervical Cancer ◽

T Cell ◽

Cell Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Correct Choice ◽

Adoptive T Cell Therapy ◽

Treatment Standards ◽

T Cell Therapy

Immunotherapy, also known as therapy with immune checkpoint inhibitors, has shown good results in the treatment of both solid tumors and hematological malignancies. Patients with diseases that were considered incurable earlier now have an opportunity for long-term disease stabilization and high frequency of clinical remissions. This review focuses on clinical benefits and toxicity profiles of immune checkpoint inhibitors used for cervical cancer, as well as on the ways to improve prognosis and indications for immunotherapy. Correct choice of biomarkers for predicting the response to immunotherapy will ensure more precise selection of patients. This review of immunotherapy methods aims to help clinicians with the indications for this relatively new treatment which has revolutionized treatment standards. Immunotherapy has many forms, including oncolytic virus therapy, chimeric antigen receptor T-cell therapy (CAR), cancer vaccines, and adoptive T-cell therapy, in particular, immune checkpoint inhibitors, first generation of which includes monoclonal antibodies against PD-1 (pembrolizumab, nivolumab, and cemiplimab), against PD-L1 (atezolizumab, avelumab, and durvalumab), and against CTLA-4 protein (ipilimumab).

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Cardiotoxicity associated with immune checkpoint inhibitors and CAR T-cell therapy

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2021.07.014 ◽

2021 ◽

Author(s):

Demis N. Lipe ◽

Eva Rajha ◽

Adriana H. Wechsler ◽

Susan Gaeta ◽

Nicolas L. Palaskas ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

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Chimeric antigen receptor T cells immunotherapy: challenges and opportunities in hematological malignancies

Immunotherapy ◽

10.2217/imt-2020-0181 ◽

2020 ◽

Vol 12 (18) ◽

pp. 1341-1357

Author(s):

Nashwa El-Khazragy ◽

Sherief Ghozy ◽

Passant Emad ◽

Mariam Mourad ◽

Diaaeldeen Razza ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Hematological Malignancies ◽

Antigen Receptor ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Challenges And Opportunities

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

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