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CHICAGO—The bispecific antibody APVO436 has demonstrated robust T-cell activation with limited cytokine release in acute myeloid leukemia (AML), according to researchers.
APVO436 binds CD123 and CD3 to redirect T-cell cytotoxicity against CD123-expressing tumor cells.
Researchers found that APVO436 induced T-cell cytotoxicity in AML cells in vitro and in mouse models.
In addition, levels of several cytokines were lower in experiments with APVO436 than in experiments with a comparator antibody.
These findings were presented in a poster at the AACR Annual Meeting 2018 (abstract 1786).
The research was conducted by employees of Aptevo Therapeutics Inc., the company developing APVO436.
“We are especially excited about these latest data for APVO436, which continue to show robust T-cell engagement and cytotoxic activity with reduced levels of cytokine release,” said Jane Gross, PhD, senior vice president and chief scientific officer for Aptevo.
Dr Gross and her colleagues found that APVO436 binds human CD123 and CD3-expressing cells and has “potent” target-specific activity against CD123-expressing AML cell lines (Molm-13 and KG-1a).
In addition, APVO436 induced endogenous T-cell activation and proliferation, accompanied by depletion of CD123-expressing cells, in samples from AML patients and healthy donors.
T cells from these cultures (both AML and non-AML) were expanded and co-cultured with Molm-13 cells and APVO436 or a control antibody. Again, the researchers observed “potent” cytotoxic activity in the presence of APVO436.
Dr Gross and her colleagues also tested APVO436, co-administered with human T cells, in mice with established disseminated Molm-13 tumors. The treatment resulted in a “rapid and significant” reduction in skeletal tumor burden.
Finally, the team compared APVO436 with an Aptevo-generated version of MGD006, a CD123 x CD3 dual-affinity re-targeting molecule being developed by Macrogenics, Inc.
The researchers took purified T cells from healthy donors and cultured them with Molm-13 cells, as well as APVO436, Aptevo’s version of MGD006, and a control antibody.
Both APVO436 and Aptevo’s version of MGD006 were effective at stimulating a tumor-directed immune response, inducing comparable levels of T-cell activation, proliferation, and cytotoxicity.
However, APVO436 induced lower levels of several cytokines—including IFNγ, IL-2, IL-6, and TNFα.
“Importantly, IFNγ, IL-6, and TNFα are considered to be the most relevant cytokines responsible for dosing toxicities observed in clinical studies with T-cell engaging molecules, which suggests that APVO436 could offer the potential for reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses,” Dr Gross said.
She added that Aptevo is planning to launch a phase 1 trial of APVO436 in patients with AML and myelodysplastic syndromes later this year.
CHICAGO—The bispecific antibody APVO436 has demonstrated robust T-cell activation with limited cytokine release in acute myeloid leukemia (AML), according to researchers.
APVO436 binds CD123 and CD3 to redirect T-cell cytotoxicity against CD123-expressing tumor cells.
Researchers found that APVO436 induced T-cell cytotoxicity in AML cells in vitro and in mouse models.
In addition, levels of several cytokines were lower in experiments with APVO436 than in experiments with a comparator antibody.
These findings were presented in a poster at the AACR Annual Meeting 2018 (abstract 1786).
The research was conducted by employees of Aptevo Therapeutics Inc., the company developing APVO436.
“We are especially excited about these latest data for APVO436, which continue to show robust T-cell engagement and cytotoxic activity with reduced levels of cytokine release,” said Jane Gross, PhD, senior vice president and chief scientific officer for Aptevo.
Dr Gross and her colleagues found that APVO436 binds human CD123 and CD3-expressing cells and has “potent” target-specific activity against CD123-expressing AML cell lines (Molm-13 and KG-1a).
In addition, APVO436 induced endogenous T-cell activation and proliferation, accompanied by depletion of CD123-expressing cells, in samples from AML patients and healthy donors.
T cells from these cultures (both AML and non-AML) were expanded and co-cultured with Molm-13 cells and APVO436 or a control antibody. Again, the researchers observed “potent” cytotoxic activity in the presence of APVO436.
Dr Gross and her colleagues also tested APVO436, co-administered with human T cells, in mice with established disseminated Molm-13 tumors. The treatment resulted in a “rapid and significant” reduction in skeletal tumor burden.
Finally, the team compared APVO436 with an Aptevo-generated version of MGD006, a CD123 x CD3 dual-affinity re-targeting molecule being developed by Macrogenics, Inc.
The researchers took purified T cells from healthy donors and cultured them with Molm-13 cells, as well as APVO436, Aptevo’s version of MGD006, and a control antibody.
Both APVO436 and Aptevo’s version of MGD006 were effective at stimulating a tumor-directed immune response, inducing comparable levels of T-cell activation, proliferation, and cytotoxicity.
However, APVO436 induced lower levels of several cytokines—including IFNγ, IL-2, IL-6, and TNFα.
“Importantly, IFNγ, IL-6, and TNFα are considered to be the most relevant cytokines responsible for dosing toxicities observed in clinical studies with T-cell engaging molecules, which suggests that APVO436 could offer the potential for reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses,” Dr Gross said.
She added that Aptevo is planning to launch a phase 1 trial of APVO436 in patients with AML and myelodysplastic syndromes later this year.
CHICAGO—The bispecific antibody APVO436 has demonstrated robust T-cell activation with limited cytokine release in acute myeloid leukemia (AML), according to researchers.
APVO436 binds CD123 and CD3 to redirect T-cell cytotoxicity against CD123-expressing tumor cells.
Researchers found that APVO436 induced T-cell cytotoxicity in AML cells in vitro and in mouse models.
In addition, levels of several cytokines were lower in experiments with APVO436 than in experiments with a comparator antibody.
These findings were presented in a poster at the AACR Annual Meeting 2018 (abstract 1786).
The research was conducted by employees of Aptevo Therapeutics Inc., the company developing APVO436.
“We are especially excited about these latest data for APVO436, which continue to show robust T-cell engagement and cytotoxic activity with reduced levels of cytokine release,” said Jane Gross, PhD, senior vice president and chief scientific officer for Aptevo.
Dr Gross and her colleagues found that APVO436 binds human CD123 and CD3-expressing cells and has “potent” target-specific activity against CD123-expressing AML cell lines (Molm-13 and KG-1a).
In addition, APVO436 induced endogenous T-cell activation and proliferation, accompanied by depletion of CD123-expressing cells, in samples from AML patients and healthy donors.
T cells from these cultures (both AML and non-AML) were expanded and co-cultured with Molm-13 cells and APVO436 or a control antibody. Again, the researchers observed “potent” cytotoxic activity in the presence of APVO436.
Dr Gross and her colleagues also tested APVO436, co-administered with human T cells, in mice with established disseminated Molm-13 tumors. The treatment resulted in a “rapid and significant” reduction in skeletal tumor burden.
Finally, the team compared APVO436 with an Aptevo-generated version of MGD006, a CD123 x CD3 dual-affinity re-targeting molecule being developed by Macrogenics, Inc.
The researchers took purified T cells from healthy donors and cultured them with Molm-13 cells, as well as APVO436, Aptevo’s version of MGD006, and a control antibody.
Both APVO436 and Aptevo’s version of MGD006 were effective at stimulating a tumor-directed immune response, inducing comparable levels of T-cell activation, proliferation, and cytotoxicity.
However, APVO436 induced lower levels of several cytokines—including IFNγ, IL-2, IL-6, and TNFα.
“Importantly, IFNγ, IL-6, and TNFα are considered to be the most relevant cytokines responsible for dosing toxicities observed in clinical studies with T-cell engaging molecules, which suggests that APVO436 could offer the potential for reduced toxicities compared to other CD123 x CD3 T-cell engagers at comparable or higher doses,” Dr Gross said.
She added that Aptevo is planning to launch a phase 1 trial of APVO436 in patients with AML and myelodysplastic syndromes later this year.