Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

McKenna, Mary K.; Englisch, Alexander; Brenner, Benjamin; Smith, Tyler S.; Hoyos, Valentina; Suzuki, Masataka; Brenner, Malcolm K.

doi:10.1016/j.ymthe.2021.02.004

Cited by 43 publications

(26 citation statements)

References 66 publications

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“…For example, Melzer et al showed that CD8+ T central memory cells (CD8+ T cm) can be efficiently loaded with VSV and transport virus to tumour cells without compromising their own viability or antitumor reactivity [55]. Furthermore, mesenchymal stromal cells have been shown to systemically deliver a binary vector containing an OAd together with a helperdependent Ad (HDAd; combinatorial Ad vector (Cad)) that expresses interleukin-12 (IL-12) and checkpoint PD-L1 (programmed death-ligand 1) blocker [56]. Alternatively, chemical agents can also be used as protective "camouflage" for OV, and this was demonstrated by Nosaki et al [50].…”

Section: Overcoming Barriers Of Intravenous Delivery Ovmentioning

confidence: 99%

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Kwan

Winder

Muthana

2021

Viruses

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Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

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Section: Overcoming Barriers Of Intravenous Delivery Ovmentioning

confidence: 99%

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Kwan

Winder

Muthana

2021

Viruses

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“…Recently, a combination of cell carrier-delivered oncolytic adenovirus (OAd) and CAR-T cells was reported to be effective against lung tumors in animal models [147]. The adenovirus was engineered to encode IL-12 and anti-PD-L1 antibodies, and mesenchymal stem cells (MSCs) were used as cell carrier, delivering and producing OAd and eradicating tumor cells.…”

Section: Combination Therapy 431 Chemotherapy or Other Strategiesmentioning

confidence: 99%

Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy

Chung

Jung

Noh

2021

IJMS

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Cancer immunotherapy is becoming more important in the clinical setting, especially for cancers resistant to conventional chemotherapy, including targeted therapy. Chimeric antigen receptor (CAR)-T cell therapy, which uses patient’s autologous T cells, combined with engineered T cell receptors, has shown remarkable results, with five US Food and Drug Administration (FDA) approvals to date. CAR-T cells have been very effective in hematologic malignancies, such as diffuse large B cell lymphoma (DLBCL), B cell acute lymphoblastic leukemia (B-ALL), and multiple myeloma (MM); however, its effectiveness in treating solid tumors has not been evaluated clearly. Therefore, many studies and clinical investigations are emerging to improve the CAR-T cell efficacy in solid tumors. The novel therapeutic approaches include modifying CARs in multiple ways or developing a combination therapy with immune checkpoint inhibitors and chemotherapies. In this review, we focus on the challenges and recent advancements in CAR-T cell therapy for solid tumors.

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“…at the single-cell level. This allows for the detection of rare highly polyfunctional cell subsets that are orchestrators of response against tumors or pathogens, and are highly correlative of response, potency, and persistence in various studies across different clinical settings [44,62,[71][72][73][74][75][76][77][78][79].…”

Section: Isolightmentioning

confidence: 99%

Single-Cell Multiomics Analysis for Drug Discovery

Nassar

Raddassi

2021

Metabolites

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Given the heterogeneity seen in cell populations within biological systems, analysis of single cells is necessary for studying mechanisms that cannot be identified on a bulk population level. There are significant variations in the biological and physiological function of cell populations due to the functional differences within, as well as between, single species as a result of the specific proteome, transcriptome, and metabolome that are unique to each individual cell. Single-cell analysis proves crucial in providing a comprehensive understanding of the biological and physiological properties underlying human health and disease. Omics technologies can help to examine proteins (proteomics), RNA molecules (transcriptomics), and the chemical processes involving metabolites (metabolomics) in cells, in addition to genomes. In this review, we discuss the value of multiomics in drug discovery and the importance of single-cell multiomics measurements. We will provide examples of the benefits of applying single-cell omics technologies in drug discovery and development. Moreover, we intend to show how multiomics offers the opportunity to understand the detailed events which produce or prevent disease, and ways in which the separate omics disciplines complement each other to build a broader, deeper knowledge base.

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Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

Cited by 43 publications

References 66 publications

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy

Single-Cell Multiomics Analysis for Drug Discovery

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