Cellular immunotherapies for cancer

Berraondo, Pedro; Labiano, Sara; Minute, Luna; Etxeberría, Iñaki; Vásquez, Marcos; Sánchez-Arráez, Álvaro; Teijeira, Álvaro; Melero, Ignacio

doi:10.1080/2162402x.2017.1306619

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…The field of immuno-oncology has experienced rapid and exciting growth, benefiting from the development of intricate adoptive cell therapies (1) and numerous mAbs (with clinical approval of over 20 of these Abs), and a deeper understanding of the immunesuppressive tumor microenvironment now deemed a hallmark of cancer (2)(3)(4). Immunotherapies, which function by priming the patient's immune system to recognize and destroy malignant cells, have greatly altered traditional treatment paradigms.…”

Section: Introductionmentioning

confidence: 99%

Imaging activated T cells predicts response to cancer vaccines

Alam¹,

Mayer²,

Sagiv-Barfi

et al. 2018

Journal of Clinical Investigation

122

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In situ cancer vaccines are under active clinical investigation, given their reported ability to eradicate both local and disseminated malignancies. Intratumoral vaccine administration is thought to activate a T cell-mediated immune response, which begins in the treated tumor and cascades systemically. In this study, we describe a PET tracer (64Cu-DOTA-AbOX40) that enabled noninvasive and longitudinal imaging of OX40, a cell-surface marker of T cell activation. We report the spatiotemporal dynamics of T cell activation following in situ vaccination with CpG oligodeoxynucleotide in a dual tumor-bearing mouse model. We demonstrate that OX40 imaging was able to predict tumor responses on day 9 after treatment on the basis of tumor tracer uptake on day 2, with greater accuracy than both anatomical and blood-based measurements. These studies provide key insights into global T cell activation following local CpG treatment and indicate that 64Cu-DOTA-AbOX40 is a promising candidate for monitoring clinical cancer immunotherapy strategies.

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Section: Introductionmentioning

confidence: 99%

Imaging activated T cells predicts response to cancer vaccines

Alam¹,

Mayer²,

Sagiv-Barfi

et al. 2018

Journal of Clinical Investigation

122

View full text Add to dashboard Cite

show abstract

“…To enhance CAR T-cell persistence and anticancer efficacy, many research teams have exploited potential therapeutic strategies to overcome the hurdles for CAR T-cell therapy in solid tumors 34 . The combination of adoptive T-cell regimen and other immunotherapies is a potentially promising strategy to overcome the unsatisfactory curative effect for solid tumors and the relapse after immune checkpoint inhibitor treatment.…”

Section: Discussionmentioning

confidence: 99%

Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

Huang

Jiang

et al. 2018

Cell Death Dis

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Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.

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“…Immunotherapy of cancer is gaining interest and impact on patient overall survival in many solid tumors. 7 In the field of HCC, nivolumab (anti-PD-1 monoclonal antibody) in second line appears to be the most promising strategy, as was observed by El-Khoueiry et al in a phase 1/2 clinical trial. 8 It is possible to increase the efficacy of checkpoint inhibitors through their combination with locoregional therapies, changing the tumor microenvironment (TME), which may have a synergistic effect or act upon mechanisms of primary or acquired resistance to checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 93%

4Mu Decreases CD47 Expression on Hepatic Cancer Stem Cells and Primes a Potent Antitumor T Cell Response Induced by Interleukin-12

et al. 2018

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The tumor microenvironment (TME) represents a complex interplay between different cellular components, including tumor cells and cancer stem cells (CSCs), with the associated stroma; such interaction promotes tumor immune escape and sustains tumor growth. Several experimental approaches for cancer therapy are focused on TME remodeling, resulting in increased antitumor effects. We previously demonstrated that the hyaluronan synthesis inhibitor 4-methylumbelliferone (4Mu) decreases liver fibrosis and induces antitumor activity in hepatocellular carcinoma (HCC). In this work, 4Mu, in combination with an adenovirus encoding interleukin-12 genes (AdIL-12), elicited a potent antitumor effect and significantly prolonged animal survival (p < 0.05) in an orthotopic HCC model established in fibrotic livers. In assessing the presence of CSCs, we found reduced mRNA levels of CD133 + , CD90 + , EpCAM + , CD44 + , and CD13 + CSC markers within HCC tumors (p < 0.01). Additionally, 4Mu downregulated the expression of the CSC marker CD47 + on HCC cells, promoted phagocytosis by antigen-presenting cells, and, combined with Ad-IL12, elicited a potent cytotoxic-specific T cell response. Finally, animal survival was increased when CD133 low HCC cells, generated upon 4Mu treatment, were injected in a metastatic HCC model. In conclusion, the combined strategy ameliorates HCC aggressiveness by targeting CSCs and as a result of the induction of anticancer immunity.

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Cellular immunotherapies for cancer

Cited by 16 publications

References 31 publications

Imaging activated T cells predicts response to cancer vaccines

Imaging activated T cells predicts response to cancer vaccines

Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

4Mu Decreases CD47 Expression on Hepatic Cancer Stem Cells and Primes a Potent Antitumor T Cell Response Induced by Interleukin-12

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