Adult Survivorship: Considerations Following CAR T-Cell Therapy

Buitrago, Joaquin; Adkins, Sherry; Hawkins, Misha; Iyamu, Kharington; Oort, Teresa van

doi:10.1188/19.cjon.s1.42-48

Cited by 9 publications

(6 citation statements)

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“…B cell aplasia may be an important complication in some patients, however in the majority of patients, including most adults, B cell aplasia is a manageable toxicity. Hematology oncologists and rheumatologists have worked with B cell depletion agents for many years and the protocols for managing B cell aplasia are well understood [55][56][57]. It is conceivable that targeting B cells in the manner described will induce clinical toxicity such as cytokine release syndrome; such toxicities related to CAR T cell activity have also become increasing manageable [58,59].…”

Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Ambrose

et al. 2020

Preprint

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Successful CAR T cell therapy for the treatment of solid tumors requires exemplary CAR T cell expansion, persistence and fitness, and the ability to target tumor antigens safely. Here we address this constellation of critical attributes for successful cellular therapy by using integrated technologies that simplify development and derisk clinical translation. We have developed a CAR-CD19 T cell that secretes a CD19-anti-Her2 bridging protein. This cell therapy strategy exploits the ability of CD19-targeting CAR T cells to interact with CD19 on normal B cells to drive expansion, persistence and fitness. The secreted bridging protein potently binds to Her2positive tumor cells, mediating CAR-CD19 T cell cytotoxicity in vitro and in vivo. Because of its short half-life, the secreted bridging protein will selectively accumulate at the site of highest antigen expression, ie. at the tumor. Bridging proteins that bind to multiple different tumor antigens have been created. Therefore, antigen-bridging CAR-CD19 T cells incorporate critical attributes for successful solid tumor cell therapy. This platform can be exploited to attack any cancer.

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Section: Discussionmentioning

confidence: 99%

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Ambrose

et al. 2020

Preprint

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“…Adoptive cellular therapies are promising salvage treatments for patients with relapsed or refractory (r/r) hematological malignancies [ 3 ]. These therapies involve T cells and natural killer cells that have been genetically modified to express CARs.…”

Section: Adoptive Cellular Therapies and Cellular Immunotherapiesmentioning

confidence: 99%

“…The likelihood of developing extended immunosuppression and off-target effects, such as B-cell aplasia leading to long-term hypogammaglobulinemia, increases with the number of previous lines of therapy [ 12 ]. This has been observed within 9 weeks following receipt of CAR T-cell infusion and may persist through 4 years [ 3 ]. In a pooled analysis of 3 clinical trials (NCT01029366 and NCT02640209 for tisagenlecleucel, and NCT01747486 for CART-19/4-1 BB) that included 67 patients who received CD19-directed CAR T-cell therapy [ 15 ], 44% of patients had hypogammaglobulinemia before therapy, and 81% developed a new or persistent decline in their immunoglobulin levels following infusion [ 15 ].…”

Section: Intermediate and Late Phasementioning

confidence: 99%

Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention

Dib

Ariza-Heredia

Spallone

et al. 2023

Open Forum Infectious Diseases

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Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T-cells, natural killer cells, and genetically modified T-cell receptors, are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventative and therapeutic options for common RVIs, and appropriate infection control and preventative strategies.

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“…Notably, T cell therapies tend to produce high levels of IL-6, leading to potentially fatal complications of cytokine release syndrome and neurotoxicity—because NK cells produce much less IL-6 than T cells, this risk is greatly diminished [ 251 , 252 ]. Because NK cells (and CLL-targeting antibodies) have a finite lifespan, there is also the potential to avoid the prolonged B cell lymphopenia and hypogammaglobulinemia seen in many patients after CD19-CAR-T therapy, although this theoretical benefit will need to be tested in clinical trials [ 253 ].…”

Section: Advantages Of Nk Therapy For Cllmentioning

confidence: 99%

Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential

Yano

Byrd

Muthusamy

2022

Cancers

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Immunotherapy approaches have advanced rapidly in recent years. While the greatest therapeutic advances so far have been achieved with T cell therapies such as immune checkpoint blockade and CAR-T, recent advances in NK cell therapy have highlighted the therapeutic potential of these cells. Chronic lymphocytic leukemia (CLL), the most prevalent form of leukemia in Western countries, is a very immunosuppressive disease but still shows significant potential as a target of immunotherapy, including NK-based therapies. In addition to their antileukemia potential, NK cells are important immune effectors in the response to infections, which represent a major clinical concern for CLL patients. Here, we review the interactions between NK cells and CLL, describing functional changes and mechanisms of CLL-induced NK suppression, interactions with current therapeutic options, and the potential for therapeutic benefit using NK cell therapies.

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Adult Survivorship: Considerations Following CAR T-Cell Therapy

Cited by 9 publications

References 0 publications

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Anti-CD19 CAR T cells potently redirected to kill solid tumor cells

Respiratory Viral Infections in Recipients of Cellular Therapies: A Review of Incidence, Outcomes, Treatment, and Prevention

Natural Killer Cells in Chronic Lymphocytic Leukemia: Functional Impairment and Therapeutic Potential

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