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Translation in Brief

Roche and Immune-Onc mAb data; plus Capricor’s exosome-based COVID-19 vaccine induces cellular immunity, and more

BioCentury’s roundup of translational news

BioCentury’s roundup of translational news.

Nov 13, 2020 | 9:48 PM GMT

Roche’s mAb depletes regulatory T cells
Roche (SIX:ROG; OTCQX:RHHBY) and University College London scientists reported in Nature Cancer that the anti-CD25 mAb RG6292, which is in a Phase I trial in advanced solid tumor patients, depleted intratumoral regulatory T cells without blocking IL-2 signaling on bystander effector T cells in human tumor samples. RG6292 also depleted Tregs and activated tumor-infiltrating CD8+ T cells in humanized tumor-bearing mouse models and nonhuman primates with no sign of toxicity.

Immune-Onc’s mAb reprograms immune cells
Immune-Onc Therapeutics Inc. presented a poster this week at The Society for Immunotherapy of Cancer (SITC) meeting showing its LILRB2 antagonist IO-108 reprograms immune suppressive myeloid cells to a pro-inflammatory state which enhances T cell activation in patient-derived solid tumor samples. The company plans to submit an IND for IO-108 in 1H21.

Capricor’s exosome-based COVID-19 mRNA vaccine induces cellular immunity
Researchers from Capricor Therapeutics Inc. (NASDAQ:CAPR) and Johns Hopkins University showed in a bioRxiv preprint that mice injected with COVID-19 vaccine LSNME/SW1 — an exosome-based mRNA vaccine that contains portions of SARS-CoV-2 S, SARS-CoV-2 N, SARS-CoV-2 M, SARS-CoV-2 E and a full-length SARS-CoV-2 S — developed SARS-CoV-2 S and SARS-CoV-2 N reactive CD4+ and CD8+ T cells. The S-reactive T cell population displayed elevated expression of Th1-associated IFNγ and Th2-associated IL-4.

SARS-CoV-2 responsive T cell number associates with likelihood of getting COVID-19
A medRxiv preprint suggests that people with higher SARS-CoV-2 T cell responses are less likely to develop COVD-19. The team, led by Public Health England scientists, used TSPOT Discovery SARS-CoV-2 kits from Oxford Immunotec Ltd. to measure T cell responsiveness to SARS-CoV-2 proteins. They found 2,016 patients with a low response and 669 patients with a high response. At a 118-day median follow-up, 20 participants with low T cell responses developed COVID-19 whereas none with high T cell responses did so.

Unique antibody signature in severe COVID-19 patients
A team led by Stanford University scientists found a unique anti-SARS-CoV-2 IgG subclass signature in severe COVID-19 patients that included increased IgG1 antibodies with reduced Fc fucosylation (high afucosylation) and elevated IgG3 antibodies. Published in Nature Immunology, the study found afucosylated SARS-CoV-2 IgGs enhanced interactions with CD16a on monocytes and promoted pro-inflammatory cytokine production.

γδ T cell engagers show early signs of efficacy
At this week’s SITC meeting, Shattuck Labs Inc. (NASDAQ:STTK) and ImCheck Therapeutics S.A.S. reported early hints of efficacy for their respective γδ T cell engaging antibodies. Shattuck demonstrated that a butyrophilin heterodimer could activate  γδ T cells in vitro and in vivo to target killing of CD19-expressing lymphoma cells, providing preclinical proof of concept for its  γδ T cell engager (GADLEN) platform. Separately, ImCheck showed monotherapy with ICT01, a γδ T cell-activating mAb, led to specific, dose-dependent γ9δ2 T cell activation without dose-limiting toxicities or treatment-related serious AEs among the first cohort of six solid tumor patients in its Phase I/IIa EVICTION trial. 

TARGETS
CD25 (IL2RA) – Interleukin-2 (IL-2) receptor α chain 
CD16a (FCGR3A; FcγRIIIa) – Fc γ receptor IIIa 
IFNγ – Interferon γ
IgG1 – Immunoglobulin G1 
IgG3 – Immunoglobulin G3
IL-2 – Interleukin-2 
IL-4 (BSF1) – Interleukin-4 
LILRB2 (LIR2) – Leukocyte immunoglobulin-like receptor subfamily B member 2 
SARS-CoV-2 E – SARS-CoV-2 envelope protein 
SARS-CoV-2 M – SARS-CoV-2 membrane protein 
SARS-CoV-2 N – SARS-CoV-2 nucleocapsid protein 
SARS-CoV-2 S – SARS-CoV-2 spike protein 

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