# Development of Novel CD180-Based Cancer Immunotherapeutics

> **NIH NIH R41** · ABACUS BIOSCIENCE INC · 2022 · $398,040

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Clark, Edward A
PROJECT SUMMARY
Abacus Bioscience focuses on developing novel and game changing immunotherapies for treating cancers
and chronic infectious diseases. We have developed a broad-based, patented, platform technology that can
plug-and-play with multiple cancer or viral antigens (Ags). We propose to establish a new class of cancer
immunotherapeutics to overcome the limitations of currently marketed checkpoint blockade inhibitor (CPI)
therapies. Many patients with cancers are immunosuppressed; the microenvironment of tumors can actively
promote immunosuppression. Although some cancer immunotherapies are quite promising, others have
significant limitations. PD-1-based checkpoint CPI therapies, for example, only induce objective clinical
responses in about half of cancer patients. Although they may release the `Brake' on the immune system,
without antigen (Ag)-specific `Ignition' and co-stimulation or innate immune `Activation', they do not promote
optimal tumor immunity. Our strategy to overcome current obstacles to cancer immunotherapy, particularly for
patients who are unable to respond to CPI therapies, is to target tumor-associated Ags to specifically-activated
immune cells. Our immunotherapeutics both `Ignite' Ag-specific immune responses and `Activate' strong and
coordinated innate immunity. We have found that Ags coupled to antibodies (Abs) specific for the CD180
(RP105) receptor (Ag-CD180) induce strong Ag-specific Ab and T cell responses and protective immunity to a
lethal viral infection. Targeting Ags to CD180 rapidly programs two major classes of Ag presenting cells
(APCs): dendritic cells (DCs), the `starting gun' APCs that activate immunity, and B cells, APCs that sustain
Ag-specific T cell immunity. The presence of B cells in cancers such as breast and ovarian cancers correlates
with a better prognosis. The presence of B cells in certain human tumors correlates with better responsiveness
to immunotherapy. The fact that CD180-based immunotherapeutics target and activate B cells to become
efficient APCs suggests that a CD180-based immunotherapeutic may be able to activate B cells in tumors and
promote anti-tumor immunity. We will test if our dual-action CD180-based immunotherapeutics can work alone
or with other immune activators including anti-PD-1 to produce effective anti-tumor immunity. We have
selected the survivin (Birc5) protein, a member of inhibitor of apoptosis family, as a tumor Ag to couple to anti-
CD180 to create the immunotherapeutic, survivin-CD180. We will design and produce survivin-anti-CD180
recombinant proteins that target either mouse or human CD180. We will test if mouse survivin-anti-CD180 can
prevent, delay or completely stop tumor growth using two mouse cancer models. If successful, these studies
will establish a new class of cancer immunotherapeutics and build a strong preclinical data package and
rationale for moving survivin-hCD180 im...

## Key facts

- **NIH application ID:** 10381384
- **Project number:** 1R41CA257531-01A1
- **Recipient organization:** ABACUS BIOSCIENCE INC
- **Principal Investigator:** Edward A Clark
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,040
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10381384

## Citation

> US National Institutes of Health, RePORTER application 10381384, Development of Novel CD180-Based Cancer Immunotherapeutics (1R41CA257531-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10381384. Licensed CC0.

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