scholarly journals Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 339 ◽  
Author(s):  
Teresa Poggio ◽  
Justus Duyster ◽  
Anna Illert
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Cell Physiology ◽  
Cell Therapies ◽  
Car T

T cell non-Hodgkin lymphoma (T-NHL) is a rare and heterogeneous group of neoplasms of the lymphoid system. With the exception of a few relatively indolent entities, T-NHL is typically aggressive, treatment resistant, and associated with poor prognosis. Relatively few options with proven clinical benefit are available for patients with relapsed or refractory disease. Immunotherapy has emerged as a promising treatment for the management of patients with hematological malignancies. The identification of tumor antigens has provided a large number of potential targets. Therefore, several monoclonal antibodies (alemtuzumab, SGN-30, brentuximab vedotin, and mogamulizumab), directed against tumor antigens, have been investigated in different subtypes of T-NHL. In addition to targeting antigens involved in cancer cell physiology, antibodies can stimulate immune effector functions or counteract immunosuppressive mechanisms. Chimeric antigen receptor (CAR)-T cells directed against CD30 and immune checkpoint inhibitors are currently being investigated in clinical trials. In this review, we summarize the currently available clinical evidence for immunotherapy in T-NHL, focusing on the results of clinical trials using first generation monoclonal antibodies, new immunotherapeutic agents, immune checkpoint inhibitors, and CAR-T cell therapies.

scholarly journals Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

2021 ◽  
Vol 7 (3) ◽  
pp. 186
Author(s):  
Ioannis Kyriakidis ◽  
Eleni Vasileiou ◽  
Claudia Rossig ◽  
Emmanuel Roilides ◽  
Andreas H. Groll ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gemtuzumab Ozogamicin ◽  
Brentuximab Vedotin ◽  
Inotuzumab Ozogamicin ◽  
Cell Therapies ◽  
Invasive Fungal Diseases ◽  
Car T

Since 1985 when the first agent targeting antigens on the surface of lymphocytes was approved (muromonab-CD3), a multitude of such therapies have been used in children with hematologic malignancies. A detailed literature review until January 2021 was conducted regarding pediatric patient populations treated with agents that target CD2 (alefacept), CD3 (bispecific T-cell engager [BiTE] blinatumomab), CD19 (denintuzumab mafodotin, B43, BiTEs blinatumomab and DT2219ARL, the immunotoxin combotox, and chimeric antigen receptor [CAR] T-cell therapies tisagenlecleucel and axicabtagene ciloleucel), CD20 (rituximab and biosimilars, 90Y-ibritumomab tiuxetan, ofatumumab, and obinutuzumab), CD22 (epratuzumab, inotuzumab ozogamicin, moxetumomab pasudotox, BiTE DT2219ARL, and the immunotoxin combotox), CD25 (basiliximab and inolimomab), CD30 (brentuximab vedotin and iratumumab), CD33 (gemtuzumab ozogamicin), CD38 (daratumumab and isatuximab), CD52 (alemtuzumab), CD66b (90Y-labelled BW 250/183), CD248 (ontuxizumab) and immune checkpoint inhibitors against CTLA-4 (CD152; abatacept, ipilimumab and tremelimumab) or with PD-1/PD-L1 blockade (CD279/CD274; atezolizumab, avelumab, camrelizumab, durvalumab, nivolumab and pembrolizumab). The aim of this narrative review is to describe treatment-related invasive fungal diseases (IFDs) of each category of agents. IFDs are very common in patients under blinatumomab, inotuzumab ozogamicin, basiliximab, gemtuzumab ozogamicin, alemtuzumab, and tisagenlecleucel and uncommon in patients treated with moxetumomab pasudotox, brentuximab vedotin, abatacept, ipilimumab, pembrolizumab and avelumab. Although this new era of precision medicine shows promising outcomes of targeted therapies in children with leukemia or lymphoma, the results of this review stress the necessity for ongoing surveillance and suggest the need for antifungal prophylaxis in cases where IFDs are very common complications.

scholarly journals Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
John Apostolidis ◽  
Ayman Sayyed ◽  
Mohammed Darweesh ◽  
Panayotis Kaloyannidis ◽  
Hani Al Hashmi
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Programmed Cell Death ◽  
B Cell ◽  
Cancer Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Cancer cells escape immune recognition by exploiting the programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) immune checkpoint axis. Immune checkpoint inhibitors that target PD-1/PD-L1 unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. Following the cancer paradigm, preliminary results of clinical trials in lymphoma have demonstrated that immune checkpoint inhibitors induce remarkable responses in specific subtypes, most notably classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, while in other subtypes, the results vary considerably, from promising to disappointing. Lymphomas that respond to immune checkpoint inhibitors tend to exhibit tumor cells that reside in a T-cell-rich immune microenvironment and display constitutive transcriptional upregulation of genes that facilitate innate immune resistance, such as structural variations of the PD-L1 locus, collectively referred to as T-cell-inflamed lymphomas, while those lacking such characteristics are referred to as noninflamed lymphomas. This distinction is not necessarily a sine qua non of response to immune checkpoint inhibitors, but rather a framework to move the field forward with a more rational approach. In this article, we provide insights on our current understanding of the biological mechanisms of immune checkpoint evasion in specific subtypes of B-cell and T-cell non-Hodgkin lymphomas and summarize the clinical experience of using inhibitors that target immune checkpoints in these subtypes. We also discuss the phenomenon of hyperprogression in T-cell lymphomas, related to the use of such inhibitors when T cells themselves are the target cells, and consider future approaches to refine clinical trials with immune checkpoint inhibitors in non-Hodgkin lymphomas.

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

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.

scholarly journals CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Delong Liu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Oncolytic Viruses ◽  
Immune Checkpoints ◽  
Car T Cell ◽  
Car T

Abstract New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibody-drug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CAR-T cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CAR-T cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a “do-not-eat-me” immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR- T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

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

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

scholarly journals Rethinking immune checkpoint blockade: ‘Beyond the T cell’

2021 ◽  
Vol 9 (1) ◽  
pp. e001460 ◽  
Author(s):  
Xiuting Liu ◽  
Graham D Hogg ◽  
David G DeNardo
Keyword(s):  
Immune System ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune system. Emerging research suggests that T cell-directed checkpoint antibodies such as anti-programmed cell death protein-1 (PD-1) or programmed death-ligand-1 (PD-L1) can impact innate immunity by both direct and indirect pathways, which may ultimately shape clinical efficacy. However, the mechanisms and impacts of these activities have yet to be fully elucidated, and checkpoint therapies have potentially beneficial and detrimental effects on innate antitumor immunity. Further research into the role of innate subsets during checkpoint blockade may be critical for developing combination therapies to help overcome checkpoint resistance. The potential of checkpoint therapies to amplify innate antitumor immunity represents a promising new field that can be translated into innovative immunotherapies for patients fighting refractory malignancies.

scholarly journals Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 678 ◽  
Author(s):  
Adrien Procureur ◽  
Audrey Simonaggio ◽  
Jean-Emmanuel Bibault ◽  
Stéphane Oudard ◽  
Yann-Alexandre Vano
Keyword(s):  
Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Mitotic Cell ◽  
Immunogenic Cell Death ◽  
Dna Damages ◽  
Multiple Tumor ◽  
Tumor Types

The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

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