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  • ||||||||||  ALKS 4230 / Alkermes, Keytruda (pembrolizumab) / Merck (MSD)
    [VIRTUAL] Clinical outcomes of ovarian cancer patients treated with ALKS 4230, a novel engineered cytokine, in combination with pembrolizumab: ARTISTRY-1 trial () -  Oct 14, 2020 - Abstract #SITC2020SITC_644;    
    P1/2
    An increase in CD3+CD8+ T cells (A, red = CD3; blue = CD8; purple = CD3+CD8+; teal = tumor marker), GranzymeB (B, red = CD8; green = granzymeB; yellow = granzymeB+CD8+; teal = tumor marker), and PD-L1 (C, red = PD-L1; blue = tumor marker) in the tumor microenvironment of a single patient was observed after the patient received monotherapy ALKS 4230 Conclusions The combination of ALKS 4230, an investigational agent, and pembrolizumab demonstrates an acceptable safety profile and provides some evidence of tumor shrinkage and disease stabilization in some patients with heavily pretreated OC. This regimen could represent a new therapeutic option for these patients.
  • ||||||||||  Keytruda (pembrolizumab) / Merck (MSD)
    [VIRTUAL] Enhanced immune responses in human breast and colon cancer following checkpoint therapy in a CD34+ stem cell humanized NCG (HuCD34NCG) mouse model () -  Oct 14, 2020 - Abstract #SITC2020SITC_500;    
    Mice were randomized into treatment groups based on tumor size, and checkpoint inhibitor antibodies were dosed twice weekly (anti-human PD-1, BioXcell clone: RMP1-14 or Keytruda; anti-human CTLA-4, BioXcell clone: BN13; and combination therapy)...These results demonstrate that HuCD34NCG are a robust and relevant host for various human cell xenotransplants to advance preclinical immuno-oncology drug development. Ethics Approval Animal studies were executed in compliance with local Charles River IACUC guidelines, IACUC number I-033.
  • ||||||||||  acarbose / Generic mfg.
    Preclinical, Journal:  The Antidiabetic Agent Acarbose Improves Anti-PD-1 and Rapamycin Efficacy in Preclinical Renal Cancer. (Pubmed Central) -  Oct 11, 2020   
    Tumors from these mice exhibited increased frequencies of CD8 T cells that retained production of IFNγ, TNFα, perforin, and granzyme B. Combining acarbose with either anti-PD-1 or the mammalian target of rapamycin inhibitor, rapamycin, significantly reduced lung metastases relative to control mice on the same therapies. Our findings in mice suggest that combining acarbose with current RCC therapeutics may improve outcomes, warranting further study to determine whether acarbose can achieve similar responses in advanced RCC patients in a safe and likely cost-effective manner.
  • ||||||||||  Journal, CAR T-Cell Therapy, Cytokine release syndrome:  Gasdermin E-mediated target cell pyroptosis by CAR T cells triggers cytokine release syndrome. (Pubmed Central) -  Oct 10, 2020   
    In patients, GSDME and lactate dehydrogenase levels are correlated with the severity of CRS. Notably, we find that the quantity of perforin/granzyme B used by CAR T cells rather than existing CD8 T cells is critical for CAR T cells to induce target cell pyroptosis.
  • ||||||||||  Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
    Journal:  A Tridimensional Model for NK Cell-Mediated ADCC of Follicular Lymphoma. (Pubmed Central) -  Oct 7, 2020   
    The effect of GA101 seems to be more pronounced as observed in vivo in a xenograft FL model. This study strongly supports the role of NK cells in FL and highlights the application of the 3D co-culture model for in vitro validation.
  • ||||||||||  Yervoy (ipilimumab) / Ono Pharma, BMS
    Clinical, Journal, Checkpoint inhibition, IO Biomarker:  Granzyme B Degraded Type IV Collagen Products in Serum Identify Melanoma Patients Responding to Immune Checkpoint Blockade. (Pubmed Central) -  Oct 3, 2020   
    In this study, we evaluated the biomarker potential of measuring granzyme B-mediated degradation of type IV collagen (C4G) in combination with a fibroblast activation biomarker (PRO-C3) non-invasively for identifying metastatic melanoma patients responding to the ICI ipilimumab...Combining high C4G with low PRO-C3 correlated with improved OS with a median OS of 796 days vs. 273 days (p = 0.0003) and an HR of 0.30 (95%CI: 0.15-0.60, p = 0.0006). In conclusion, these results suggest that high granzyme B degraded type IV collagen (C4G) combined with low PRO-C3 quantified non-invasively has the potential to identify the responders to ICI therapy.
  • ||||||||||  Avastin (bevacizumab) / Roche
    [VIRTUAL] Dynamic changes of PD-L1 and T-cell activation in ECLIPSE: A phase II study investigating preoperative immune combination strategies in untreated, operable ER+ primary breast cancer (Channel 2) -  Oct 2, 2020 - Abstract #SABCS2020SABCS_1304;    
    P2
    Background : Whilst Atezolizumab + nab-paclitaxel is the new standard of care in patients with PD-L1+ metastatic triple negative breast cancer (BC), the role of immunotherapy in ER+ BC has yet to be defined...Methods : Patients with histologically confirmed, untreated, operable ER+/HER2- primary BC received 1 cycle of atezolizumab alone or atezolizumab + ipatasertib, atezolizumab + cobimetinib, or atezolizumab + cobimetinib + bevacizumab 3 weeks prior to surgery or neoadjuvant therapy...Conclusions : Our data indicate that short-term induction treatment with atezolizumab ± targeted treatments induce dynamic changes toward inflamed immune phenotypes both at the morphological and transcriptional level, in patients with operable ER+/HER2- primary BC. These findings might help identify novel immunotherapy combination strategies in this setting, alongside the most appropriate biomarkers that can aid in identifying patients most likely to benefit from these treatments.
  • ||||||||||  Journal:  Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller. (Pubmed Central) -  Oct 2, 2020   
    P1
    This article is a U.S. Government work and is in the public domain in the USA. These results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways.
  • ||||||||||  Clinical, Journal:  Effects of Epstein-Barr virus infection on liver function in children. (Pubmed Central) -  Oct 2, 2020   
    These results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways. Therefore, EB virus may affect liver function by acting CD8+T lymphocytes in children.
  • ||||||||||  Journal, IO Biomarker:  MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma. (Pubmed Central) -  Oct 1, 2020   
    Using mimics, we found that miRNAs enriched in exosomes-such as Homo sapiens (hsa)-miR-3187-3p, hsa-miR-498, hsa-miR-122, hsa-miR149, and hsa-miR-181a/b -regulate TCR signaling and TNFα secretion. Our observations suggest that miRNAs in melanoma-derived exosomes aid tumor immune evasion and could be a therapeutic target.
  • ||||||||||  Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker:  Immune-Related Gene Expression and Cytokine Secretion Is Reduced Among African American Colon Cancer Patients. (Pubmed Central) -  Sep 30, 2020   
    Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches.
  • ||||||||||  Clinical, Journal, PD(L)-1 Biomarker, IO Biomarker:  Young Adult Binge Drinkers Have Immunophenotypical Disarrangements In Peripheral Natural Killer Cells. (Pubmed Central) -  Sep 26, 2020   
    Moreover, the increase found in CCR5 and PD-1 expression was correlated to the number of drinks in last occasion. Our findings show that young binge drinkers have different immunoprofiles that could suggest an early status of immunosupression and trafficking of NKC to the liver, that could be related to the onset of primeval liver damage.
  • ||||||||||  Journal:  Immunosuppressive immature myeloid cell generation is controlled by glutamine metabolism in human cancer. (Pubmed Central) -  Sep 26, 2020   
    Moreover, inhibition of glutaminase GLS1 enhanced the therapeutic efficacy of anti-PD-L1 treatment, with reduced arginase 1+ myeloid cells, increased CD8+, IFN-γ+ and Granzyme B+ T cells, and delayed tumor growth in an ICB-resistant mouse model. Our work identified a novel regulatory mechanism of glutamine metabolism in controlling the generation of suppressive IMCs in the TME.
  • ||||||||||  CP-31398 / Pfizer
    Journal, IO Biomarker:  The pharmalogical reactivation of p53 function improves breast tumor cell lysis by granzyme B and NK cells through induction of autophagy. (Pubmed Central) -  Sep 25, 2020   
    This CP31398-induced autophagy sequestrates in autophagosomes several anti-apoptotic proteins, including Bcl-X and XIAP, facilitating Granzyme B-mediated mitochondrial outer membrane permeabilization, caspase-3 activation and Granzyme B- or NK cell-induced apoptosis. Together, our results define a new way to increase cytotoxic lymphocyte-mediated lysis of p53-mutated breast cancer cell, through a p53-dependent autophagy induction, with potential applications in combined immunotherapeutic approaches.