Immunotherapies: Exploiting the Immune System for Cancer Treatment

Koury, Jeffrey; Lucero, Mariana; Cato, Caleb; Chang, Lawrence; Geiger, Joseph; Henry, Denise; Hernández, Jennifer; Hung, Fion; Kaur, Puneet; Teskey, Garrett; Tran, Andrew

doi:10.1155/2018/9585614

Cited by 104 publications

(63 citation statements)

References 131 publications

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“…Immunotherapies have come to stay in the treatment of advanced melanoma due to their improved efficacy that has translated into superior overall survival compared to conventional therapies such as chemotherapy [1]. From the recent plethora of novel immune therapies, the checkpoints inhibiting monoclonal antibodies, anti-PD1 and anti-CTLA4 have been promising in the treatment of metastatic melanoma [2,3], whereas many other are currently undergoing early clinical trials [4].…”

Section: Introductionmentioning

confidence: 99%

Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients

Kasanen

Hernberg

Mäkelä

et al. 2020

Cancer Immunol Immunother

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Anti-PD1 treatment has improved the survival of metastatic melanoma patients, yet it is unknown which patients benefit from the treatment. In this exploratory study, we aimed to understand the effects of anti-PD1 therapy on the patients' immune system and discover the characteristics that would result in successful treatment. We collected peripheral blood (PB) samples from 17 immuno-oncology-naïve metastatic melanoma patients before and after 1 and 3 months of anti-PD1 therapy. In addition, matching tumor biopsies at the time of diagnosis were collected for tissue microarray. The complete blood counts, PB immunophenotype, serum cytokine profiles, and tumor-infiltrating lymphocytes were analyzed and correlated with the clinical data. Patients were categorized based on their disease control into responders (complete response, partial response, stable disease > 6 months, N = 11) and non-responders (progressive disease, stable disease ≤ 6 months, N = 6). During therapy, the PB natural killer T (NKT) cell frequency, expression of CD25 and CD45RO on cytotoxic natural killer (NK) cells, and serum CXC chemokine levels were significantly increased in responders. Furthermore, higher age together with age-associated characteristics from PB, lower frequency of PB-naïve CD8 + T cells, and elevated levels of serum MCP-4 and OPG were discovered as baseline predictors of treatment response. We therefore propose that in addition to T cells, anti-PD1 treatment is associated with NK-and NKT-cell population dynamics, and that the age-associated characteristics from PB together with older age may contribute to prolonged PFS in anti-PD1-treated melanoma patients.

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Section: Introductionmentioning

confidence: 99%

Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients

Kasanen

Hernberg

Mäkelä

et al. 2020

Cancer Immunol Immunother

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“…As the use of checkpoint inhibitor therapy becomes more prevalent and a new generation of checkpoint inhibitors is developed, additional irAEs are likely to be recognized. 2 The study patient had a significant clinical and radiographic response to glucocorticoid therapy along with cessation of exposure to the offending antigenic source (ie, her parrot) for the hypersensitivity pneumonitis. A prolonged course of corticosteroids, usually initiated at 1 to 2 mg/kg of prednisone and tapered over the course of at least 4 to 6 weeks, is the cornerstone of therapy for moderate to severe immunerelated pulmonary toxicities.…”

Section: Discussionmentioning

confidence: 99%

“…Checkpoint inhibitors block this PD-1 and PDL-1 interaction, resulting in demonstrable antitumor effects. 2 Nivolumab and pembrolizumab are two PD-1-targeted monoclonal antibodies that have been approved for the management of advanced melanoma and for previously treated non-small cell lung cancer. 3,4 The use of checkpoint inhibitors in cancer therapy has been associated with a unique spectrum of adverse effects termed immunerelated adverse events (irAEs).…”

mentioning

confidence: 99%

Exacerbation of Previously Undiagnosed Bird Fancier’s Lung by Pembrolizumab Therapy

Vassallo

Ryu

2019

Chest

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Immune checkpoint inhibitors have revolutionized cancer therapy. As the use of checkpoint inhibitors becomes widespread, the early recognition and treatment of their unique spectrum of adverse effects, called immune-related adverse events, become critical. Perhaps the most significant of these is the pulmonary toxicity currently described as "pneumonitis." However, little is known about the effects of immune checkpoint inhibitors on preexisting interstitial lung disease. We present a case of subclinical hypersensitivity pneumonitis that was exacerbated by pembrolizumab, a programmed cell death-1 inhibitor. This case illustrates a new immunerelated adverse event and suggests that exacerbation of preexisting interstitial lung disease is a potential pulmonary toxicity from immune checkpoint inhibitor therapy.

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“…Appendix A shows some mathematical results on existence, uniqueness and positiveness of the solutions of system (1a)-(1e). (1). Mature B lymphocytes are generated from the CD19 − hematopoietic stem cells (HSCs) and through differentiation of immature CD19 + progenitors with characteristic lifetimes τ P and τ I , respectively.…”

Section: Basic Mathematical Modelmentioning

confidence: 99%

CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models

León-Triana¹,

Sabir

Calvo

et al. 2020

Preprint

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Immunotherapies use components of the patient immune system to selectively target cancer cells. The use of CAR T cells to treat B-cell malignanciesleukaemias and lymphomas-is one of the most successful examples, with many patients experiencing long-lasting complete responses to this therapy. This treatment works by extracting the patient's T cells and adding them the CAR group, which enables them to recognize and target cells carrying the antigen CD19 + , that is expressed in these haematological tumors.Here we put forward a mathematical model describing the time response of leukaemias to the injection of CAR T-cells. The model accounts for mature and progenitor B-cells, tumor cells, CAR T cells and side effects by incorporating the main biological processes involved. The model explains the early post-injection dynamics of the different compartments and the fact that the number of CAR T cells injected does not critically affect the treatment outcome. An explicit formula is found that provides the maximum CAR T cell 1 These two authors contributed equally to this work.

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Immunotherapies: Exploiting the Immune System for Cancer Treatment

Cited by 104 publications

References 131 publications

Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients

Age-associated changes in the immune system may influence the response to anti-PD1 therapy in metastatic melanoma patients

Exacerbation of Previously Undiagnosed Bird Fancier’s Lung by Pembrolizumab Therapy

CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models

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