Multipurpose, second-generation CTLA-4

AGEN1181 is a multipurpose, second-generation “Fc-engineered” anti-CTLA-4 antibody with enhanced tumor fighting abilities, designed to generate responses in a larger number of patients and improve immunogenicity.

AGEN1181, has achieved complete and partial responses, alone and in combination with AGEN’s anti-PD-1 (balstilimab / AGEN2034) in early clinical trials (as of April 2020).

Discovery of AGEN1181 and its Mechanism of Action

Agenus scientists discovered a new mechanism of action in which a specialized domain of the antibody engages with receptors on other immune cells to significantly bolster antitumor immunity. This discovery was published in Cancer Cell.

To develop AGEN1181, Agenus leveraged the above discovery to modify a part of the antibody known as the Fc region, which interacts with other immune cells to enhance antitumor immunity. In pre-clinical studies, this “Fc-engineered” antibody significantly improved the cross-talk between antigen presenting cells (APCs) and T cells. In cancer immunotherapy, such an interaction is necessary to mount a potent immune response against cancer.

Latest Clinical Trials

Solid tumors


Phase 1, multicenter study to evaluate the safety, tolerability, PK, and PD profiles of a novel Fc-engineered IgG1 anti-CTLA-4 human monoclonal antibody (AGEN1181) monotherapy and in combination with a human monoclonal IgG4 antibody (AGEN2034)

Latest Publications and Abstracts

Society for Immunotherapy of Cancer (SITC)

November 10-14, 2021

AGEN1181, an Fc-enhanced anti-CTLA-4 antibody, alone and in combination with balstilimab (anti-PD-1) in patients with advanced solid tumors: Initial phase I results. El-Khoueiry, et al.

American Association for Cancer Research (AACR)

April 9-14, 2021

Fc-enhanced anti-CTLA-4 Antibody, AGEN1181: New Mechanistic Insights for Potent Antitumor Immunity and Combination Potential in Treatment-resistant Solid Tumors. Tanne, et al.

American Association for Cancer Research (AACR)

April 9-14, 2021

Characterization of The Pharmacodynamic Activity of AGEN1181, an Fc-enhanced CTLA-4 Antibody, Alone and in Combination With the PD-1 Antibody Balstilimab. Shapiro, et al.

Society for Immunotherapy of Cancer (SITC)

November 9-14, 2020

AGEN1181, an Fc engineered anti-CTLA-4 antibody, demonstrates clinical activity, alone or in combination with balstilimab (anti-PD-1), and broadens the therapeutic potential of CTLA-4 therapy. O'Day, et al.

American Association for Cancer Research (AACR)

June 22-24, 2020

Expanding the Therapeutic Potential of anti-PD-1 and anti-CTLA-4 Therapy with Innovative Fc Engineering and Rationale Combinations for the Treatment of Solid Tumors. Tanne, et al.

American Society of Clinical Oncology (ASCO)

May 29-31, 2020

AGEN1181, a Clinical Stage Fc-Engineered anti-CTLA-4 Antibody with Improved Therapeutic Potential for the Treatment of Patients with Advanced Malignancies. O'Day, et al.

Protein and Antibody Engineering Summit (PEGS)

November 18, 2019

New mechanistic insights from TME reconditioning by an Fc engineered anti-CTLA-4 antibody. Vincent, et al.

Cancer Cell

June 11, 2018

Selective FcgR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens. Waight, et al.