Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy

Komorowski, Marcin; McGray, AJ Robert; Kołakowska, Agnieszka; Eng, Kevin H.; Gil, M. Pilar; Opyrchal, Mateusz; Litwińska, B; Nemeth, Michael J.; Odunsi, Kunle; Kozbor, Danuta

doi:10.1038/mto.2016.34

Cited by 23 publications

(26 citation statements)

References 64 publications

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“…CXCR4 antagonist plerixafor combined with anti-PD-1 therapy showed the most pronounced tumor growth delay, and was associated with increased intratumoral penetration and activation of CD8 + T lymphocytes (241). A novel strategy for the treatment of drug-resistant ovarian cancer combines chemotherapy to increase immunogenic cell death and virally delivered CXCR4 to reverse the immunosuppressive tumor microenvironment (242). Ovarian cancer of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin were infected with oncolytic vaccinia virus expressing a CXCR4 antagonist and were +/– treated in combination with doxorubicin.…”

Section: Physiologic Role Of Cxcr4 In the Immune Systemmentioning

confidence: 99%

“…Antitumor immune responses in this model culminated in the control of metastatic tumor growth and tumor-free survival. Mechanistically, the authors showed combination treatment increased apoptosis and phagocytosis of tumor material by DCs which efficiently induced adaptive antitumor immunity, reflected by increased intratumoral infiltration of antitumor CD8 + T cells and reduced immunosuppressive Tregs (242). Based on these results (Figure 2), the MORPHEUS clinical trials were started including treatment arms combining immune-checkpoint inhibitors with CXCR4 inhibition (NCT03193190, NCT03281369 and NCT03337698 for pancreatic cancer, gastric cancer and non-small cell lung cancer, respectively).…”

Section: Physiologic Role Of Cxcr4 In the Immune Systemmentioning

confidence: 99%

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Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

Schilbach²,

et al. 2018

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Cancer immunotherapy has been established as standard of care in different tumor entities. After the first reports on synergistic effects with radiotherapy and the induction of abscopal effects—tumor shrinkage outside the irradiated volume attributed to immunological effects of radiotherapy—several treatment combinations have been evaluated. Different immunotherapy strategies (e.g., immune checkpoint inhibition, vaccination, cytokine based therapies) have been combined with local tumor irradiation in preclinical models. Clinical trials are ongoing in different cancer entities with a broad range of immunotherapeutics and radiation schedules. SDF-1 (CXCL12)/CXCR4 signaling has been described to play a major role in tumor biology, especially in hypoxia adaptation, metastasis and migration. Local tumor irradiation is a known inducer of SDF-1 expression and release. CXCR4 also plays a major role in immunological processes. CXCR4 antagonists have been approved for the use of hematopoietic stem cell mobilization from the bone marrow. In addition, several groups reported an influence of the SDF-1/CXCR4 axis on intratumoral immune cell subsets and anti-tumor immune response. The aim of this review is to merge the knowledge on the role of SDF-1/CXCR4 in tumor biology, radiotherapy and immunotherapy of cancer and in combinatorial approaches.

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Section: Physiologic Role Of Cxcr4 In the Immune Systemmentioning

confidence: 99%

Section: Physiologic Role Of Cxcr4 In the Immune Systemmentioning

confidence: 99%

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

Schilbach²,

et al. 2018

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“…The potential of combining VACV with ICD inducers has been explored for drug-resistant ovarian cancers. Komorowski et al (110) combined recombinant VACV with doxorubicin, a standard of care anthracycline. In vitro treatment of ovarian cancer cells with VACV enhanced susceptibility to doxorubicin, likely mediated through type I IFNs, and increased DC tumor Ag uptake.…”

Section: Ovs: Anticancer Vaccines and Icd Inducersmentioning

confidence: 99%

Critical Interactions between Immunogenic Cancer Cell Death, Oncolytic Viruses, and the Immune System Define the Rational Design of Combination Immunotherapies

Vloten

Workenhe

Wootton

et al. 2018

The Journal of Immunology

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Oncolytic viruses (OVs) are multimodal cancer therapeutics, with one of their dominant mechanisms being in situ vaccination. There is a growing consensus that optimal cancer therapies should generate robust tumor-specific immune responses. Immunogenic cell death (ICD) is a paradigm of cellular demise culminating in the spatiotemporal release of danger-associated molecular patterns that induce potent anticancer immunity. Alongside traditional ICD inducers like anthracycline chemotherapeutics and radiation, OVs have emerged as novel members of this class of therapeutics. OVs replicate in cancers and release tumor Ags, which are perceived as dangerous because of simultaneous expression of pathogen-associated molecular patterns that activate APCs. Therefore, OVs provide the target Ags and danger signals required to induce adaptive immune responses. This review discusses why OVs are attractive candidates for generating ICD, biological barriers limiting their success in the clinic, and groundbreaking strategies to potentiate ICD and antitumor immunity with rationally designed OV-based combination therapies.

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“…For example, the systemic delivery of a vaccinia OV armed with a CXCR4 antagonist to mice with orthotopic mammary tumours disrupted the interaction between tumour cell CXCR4 and CXCL-12 present in the stromal microenvironment. This lead to tumour growth retardation, a reduction of spontaneous metastasis, the destruction of tumour associated vasculature and increased overall tumour-free survival [ 129 ].…”

Section: Potential Approaches To Combine Oncolytic Virotherapy With Cmentioning

confidence: 99%

Prospects for combined use of oncolytic viruses and CAR T-cells

Ajina

Maher

2017

j. immunotherapy cancer

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With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful. This Review draws upon recent advances in the design of novel oncolytic viruses and CAR T-cells and provides a comprehensive overview of the synergistic potential of combination oncolytic virotherapy with CAR T-cell adoptive cell transfer for the management of solid tumours, drawing particular attention to the methods by which recombinant oncolytic viruses may augment CAR T-cell trafficking into the tumour microenvironment, mitigate or reverse local immunosuppression and enhance CAR T-cell effector function and persistence.

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Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy

Cited by 23 publications

References 64 publications

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer

Critical Interactions between Immunogenic Cancer Cell Death, Oncolytic Viruses, and the Immune System Define the Rational Design of Combination Immunotherapies

Prospects for combined use of oncolytic viruses and CAR T-cells

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