Sweet Immune Checkpoint Targets to Enhance T Cell Therapy

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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Combination Strategies for Immune-Checkpoint Blockade and Response Prediction by Artificial Intelligence

International Journal of Molecular Sciences ◽

10.3390/ijms21082856 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2856 ◽

Cited By ~ 5

Author(s):

Florian Huemer ◽

Michael Leisch ◽

Roland Geisberger ◽

Thomas Melchardt ◽

Gabriel Rinnerthaler ◽

...

Keyword(s):

Artificial Intelligence ◽

T Cell ◽

Cell Therapy ◽

B Cell ◽

Immune Checkpoint ◽

T Cell Therapy ◽

Car T Cell ◽

Combination Strategies ◽

Car T Cell Therapy ◽

Car T

The therapeutic concept of unleashing a pre-existing immune response against the tumor by the application of immune-checkpoint inhibitors (ICI) has resulted in long-term survival in advanced cancer patient subgroups. However, the majority of patients do not benefit from single-agent ICI and therefore new combination strategies are eagerly necessitated. In addition to conventional chemotherapy, kinase inhibitors as well as tumor-specific vaccinations are extensively investigated in combination with ICI to augment therapy responses. An unprecedented clinical outcome with chimeric antigen receptor (CAR-)T cell therapy has led to the approval for relapsed/refractory diffuse large B cell lymphoma and B cell acute lymphoblastic leukemia whereas response rates in solid tumors are unsatisfactory. Immune-checkpoints negatively impact CAR-T cell therapy in hematologic and solid malignancies and as a consequence provide a therapeutic target to overcome resistance. Established biomarkers such as programmed death ligand 1 (PD-L1) and tumor mutational burden (TMB) help to select patients who will benefit most from ICI, however, biomarker negativity does not exclude responses. Investigating alterations in the antigen presenting pathway as well as radiomics have the potential to determine tumor immunogenicity and response to ICI. Within this review we summarize the literature about specific combination partners for ICI and the applicability of artificial intelligence to predict ICI therapy responses.

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Special delivery by “armored” CAR-T

Science Translational Medicine ◽

10.1126/scitranslmed.aav0334 ◽

2018 ◽

Vol 10 (457) ◽

pp. eaav0334

Author(s):

Steven M. Jay

Keyword(s):

T Cell ◽

Side Effects ◽

Cell Therapy ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Antitumor Efficacy ◽

T Cell Therapy ◽

Car T Cell Therapy ◽

Car T

The integration of immune checkpoint blockade with CAR-T cell therapy improves antitumor efficacy with potential for reduced side effects.

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

Current Cardiology Reports ◽

10.1007/s11886-021-01440-3 ◽

2021 ◽

Vol 23 (3) ◽

Author(s):

Ashley F. Stein-Merlob ◽

Michael V. Rothberg ◽

Patrick Holman ◽

Eric H. Yang

Keyword(s):

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

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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