Article Text

Download PDFPDF

325 Immunotherapy with B cell activating antibody CPI-006 in patients (pts) with mild to moderate COVID-19 stimulates anti-SARS-CoV-2 antibody response, memory B cells and memory T effector cells
  1. Gerard Criner1,
  2. Mehrdad Mobasher2,
  3. Craig Hill2,
  4. Shenshen Hu2,
  5. Suresh Mahabhashyam2,
  6. Joshua Brody3,
  7. Thomas Marron3,
  8. Stephen Willingham2 and
  9. Richard Miller2
  1. 1Temple University Hospital, Philadelphia, USA
  2. 2Corvus Pharmaceuticals Inc, Burlingame, CA, USA
  3. 3Icahn School of Medicine at Mount Sinai, New York, NY, USA


Background CD73 is present on subsets of B and T cells and is involved in lymphocyte activation. CPI-006 is a humanized IgG1, Fcγ receptor deficient anti-CD73 that has agonistic properties. In vitro studies and ongoing cancer clinical trials show that CPI-006 binds to B cells leading to expression of CD69, trafficking to lymph nodes, immunoglobulin class switching, transformation to plasmablasts and generation of memory B cells.1 Recently, a patient in the cancer trial with asymptomatic COVID-19 developed high titers of neutralizing anti-SARS-CoV-2 antibodies following administration of CPI-006. A phase 1 trial in COVID-19 was initiated to evaluate the use of CPI-006 to enhance anti-viral immune response (NCT04464395).

Methods Single intravenous dose escalation with N=5 per cohort of 0.3, 1.0, 3.0 and 5.0 mg/kg. Pt eligibility included PCR positive nasal swab for COVID-19; hospitalized with O2 saturation of ≥92% on <5 l/min of O2. Pts received standard care for COVID-19. Pts were monitored for safety, COVID-19 symptoms, inflammatory markers and anti-SARS-CoV-2 antibodies by ELISA. Immunophenotyping of blood by flow cytometry was performed.

Results 10 pts have been treated in the first 2 cohorts; median age 64 (range 28–76) and all had comorbidities: diabetes (4), hypertension (2), obesity (7) and/or cancer (2). Median duration of symptoms prior to CPI-006 was 8 days (range 1–21 days). No treatment-related adverse events were reported. There was no correlation between duration of symptoms and baseline anti-viral titers. Kinetics of anti-SARS-CoV-2 response to spike protein are shown for 7 pts with follow-up ≥ 7 days post CPI-006 (figure 1). One pt with lymphopenia (600/mm3) had delayed response to CPI-006; all other pts generated antibody response by Day 7 post-CPI-006 to both spike and RBD. Increasing titers of IgG and IgM antibodies were observed out to 28 days post treatment. In one pt examined, memory B cells increased from 1.81% to 4.83% of B cells 28 days after treatment with serum IgG titers to spike and to RBD of >1:50,000. 2 of 2 pts had increase in both CD4 and CD8 T effector memory cells at day 28. All pts were discharged (median 4 days) with clinical improvement.

Abstract 325 Figure 1

Antibody responses to SARS-CoV-2 spike protein in patients treated with CPI-006

Conclusions CPI-006 is well tolerated in COVID-19 pts. Low baseline titers of antibodies to virus were increased following CPI-006 in all treated pts. Immunomodulation with CPI-006 represents a novel therapy for COVID-19 aimed at stimulating more robust and prolonged anti-SARS-CoV-2 immunity potentially after infection or with vaccination.

Trial Registration NCT04464395

Ethics Approval The study was approved by Temple University Hospital’s Ethics Board, Western IRB, approval number 1-1317457-1.


  1. Luke J, Powderly J, Merchan J, Barve M, Hotson A, Mobasher M, Kwei L, Luciano G, Buggy J, Piccione E, Miller R. Immunobiology, preliminary safety, and efficacy of CPI-006, an anti-CD73 antibody with immune modulating activity, in a phase 1 trial in advanced cancers. J Clin Oncol 2019; 37:15 suppl, 2505.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.