Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone

We describe a case series of nine patients with metastatic melanoma and injectable lesions who developed progressive disease under a PD-1 inhibitor monotherapy. At the time of progressive disease, patients received intratumoral IL-2 treatment in addition to PD-1 inhibitor therapy. Three patients showed complete, three patients partial response and three patients progressive disease upon this combination therapy. IHC stainings were performed from metastases available at baseline (start of PD-1 inhibitor) and under combination therapy with IL-2. IHC results revealed a significant increase of CD4+ and CD8+ T cells and a higher PD-1 expression in the inflammatory infiltrate of the tumor microenvironment in metastases from patients with subsequent treatment response. All responding patients further showed a profound increase of the absolute eosinophil count (AEC) in the blood. Our case series supports the concept that patients with initial resistance to PD-1 inhibitor therapy and injectable lesions can profit from an additional intralesional IL-2 therapy which was well tolerated. Response to this therapy is accompanied by increase in AEC and a strong T cell-based inflammatory infiltrate.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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ConclusionThe new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R− and hGM-CSF) has entered clinical development alone and in combination ...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: These finding suggest that Poly-ICLC could be safely used for inducing transient innate immune responses in treated HIV+ subjects indicating promise as an adjuvant for HIV therapeutic vaccines. Trial Registration: www.ClinicalTrials.gov, identifier: NCT02071095. Introduction Innate immune dysregulation during HIV infection hinders the formation of anti-HIV adaptive immunity (1–6) resulting in rampant viral dissemination and progression to AIDS. Adherence to combination anti-retroviral therapy (cART) regimens controls viremia, restores CD4+T cell counts and reverses immune dysfunction to a larg ext...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionThis case highlights the complexities of care of patients with coexistent cancers, demonstrates rapid progression of primary cutaneous ALCL on nivolumab and introduces a novel adverse effect of Talimogene laherparepvec.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Conclusion: These insights may further inform the development of policies or procedures to incorporate talimogene laherparepvec into clinical settings and improve patient outcomes. PMID: 30210146 [PubMed]
Source: Herpes - Category: Infectious Diseases Authors: Tags: Hosp Pharm Source Type: research
In this study, a checkpoint blockade vaccine for canine melanoma was tested for safety and immunogenicity. Five healthy adult dogs received a mixture of three replication-defective chimpanzee-derived adenoviral vectors, one expressing mouse fibroblast-associated protein (mFAP) and the others expressing canine melanoma-associated antigens Trp-1 or Trp-2 fused into Herpes Simplex-1 glycoprotein D, a checkpoint inhibitor of herpes virus entry mediator (HVEM) pathways. The vaccine mixture was shown to be well tolerated and increased frequencies of canineTrp-1-specific activated CD8+ and CD4+ T cells secreting interferon-(IFN)-...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Over the recent years, there have been great advances in the treatment options for metastatic melanoma, which was historically a poor disease, with virtually no viable treatment options. Since 2010 –2011, this has dramatically changed with the introduction of targeted therapies and immune checkpoint blockade. Another recent breakthrough has been the approval of a first oncolytic viral immunotherapy. Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1, which can be adm inistered intralesionally in cutaneous, subcutaneous (s.c.) or lymph nodes of unresectable melanoma patients at stage IIIB/C&nd...
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Letter to the Editor Source Type: research
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