Abstract 3920
Background
B-cell maturation antigen (BCMA) is a potential therapeutic target in treatment of patients with MM. BCMA is widely expressed at the surface of myeloma cells and induces proliferative signals. BCMA-directed BCMA antibody conjugated with toxin has recently demonstrated outstanding anti-tumor responses and acceptable tolerability in MM treatment, allowing patients to achieve deeper responses with minimally added toxicity.
Methods
We used ELISA and FACS to verify AP163 can be combined with CD3/BCMA protein on the cell surface. We used the reporter gene method to verify that it induced T cell activation and target cell killing. In vivo, efficacy was studied in NCI-H929 and Raji xenograft models in female NPG mice. NPG mice were injected subcutaneously into the right dorsal flank with NCI-H929/Raji cells and human PBMC. Then the mice were treated with AP163 and tumor volume was measured twice/week. Cynomolgus monkeys were mainly used for toxicity testing. Intravenous administration is consistent with clinical administration. Its main toxicological target is the increase of cytokines and a series of adverse reactions.
Results
we constructed AP163 which binds to BCMA-expressing cell lines. AP163 induced both types of cell crosslinking, followed by T cell activation, cytokine production, proliferation and redirected target cell killing, with EC50 values in the picomolar range. The affinities of AP163 with human and cynomolgus CD3 are comparable. In vitro, AP163 only induced minimal cytokine release in the presence of BCMA target. When administered to mice bearing human MM xenografts and human T cells, AP163 eradicated subcutaneous tumors in two xenograft models tested and significantly delayed tumor growth at doses as low as 0.04mg/kg. AP163 displayed a 9-h half-life in cynomolgus and was well tolerated in non-human primates, even at high doses up to 5 mg/kg.
Conclusions
AP163 clears tumor cells in a BCMA+ and T-cell dependent manner in vitro and in vivo. Our preclinical data suggest that AP163 induces less cytokine secretion than a conventional bispecific in vitro, with reduction of tumor cell in vivo. AP163 is highly efficacious, safe and convenient for the treatment of patients with MM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
National Engineering Laboratory of High Level Expression In Mammalian Cells.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5437 - Salivary cytokines and oral mucosa cells apoptosis in patients during hematopoietic cell transplantation: possible relationship with oral mucositis
Presenter: Luciana Corrêa
Session: Poster Display session 1
Resources:
Abstract
1483 - A randomized trial of sodium alginate prevention of radiation-induced esophagitis in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy: OLCSG1401
Presenter: Toshihide Yokoyama
Session: Poster Display session 1
Resources:
Abstract
2047 - Taste and smell alterations (TSAs) in patients (pts) with stage II-III colon cancer (CC): a pilot within the PROTECT study
Presenter: Jeroen Derksen
Session: Poster Display session 1
Resources:
Abstract
5984 - Clinical characteristics are associated with acupuncture treatment response for xerostomia in cancer patients
Presenter: Wenli Liu
Session: Poster Display session 1
Resources:
Abstract
2845 - Psychosocial Distress of Adolescent and Young Adults with Cancer at Diagnosis: A Case-Matched Retrospective Cohort of 2045 Patients in British Columbia.
Presenter: Alannah Smrke
Session: Poster Display session 1
Resources:
Abstract
724 - Accuracy of distress thermometer to measure cancer-related mood disorders in Chinese patients with cancer
Presenter: Sudip Thapa
Session: Poster Display session 1
Resources:
Abstract
2357 - Modalities of biosimilar filgrastim use in clinical practice in >1000 patients receiving chemotherapy regimens with a rest period of ≤14 days: the TOPAZE study
Presenter: Jean Marc Phelip
Session: Poster Display session 1
Resources:
Abstract
1426 - The Effect of Increasing Doses of Pegfilgrastim (Peg) on Thrombocytopenia (T) in Breast Cancer (BC) Patients (pts) Receiving Taxotere (Doc), Doxorubicin, Cyclophosphamide (TAC) and Plinabulin (Plin)
Presenter: Douglas Blayney
Session: Poster Display session 1
Resources:
Abstract
712 - The use of intravenous ferric carboxymaltose without erythropoiesis-stimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy
Presenter: Hikmat Abdel-Razeq
Session: Poster Display session 1
Resources:
Abstract
1496 - Randomized, double-blind, cross-over Phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references
Presenter: Maria Velinova
Session: Poster Display session 1
Resources:
Abstract