The Inaugural International Cancer Immunotherapy Conference commenced September 16, 2015, in New York City, and one presentation detailed Biothera's new biomarker strategy in patient selection for the company's investigational cancer immunotherapy, Imprime PGG.
Jeremy Graff, PhD
The Inaugural International Cancer Immunotherapy Conference commenced September 16, 2015, in New York City, and one presentation detailed Biothera's new biomarker strategy in patient selection for the company's investigational cancer immunotherapy, Imprime PGG. Biothera researchers found that anti-β-glucan antibodies, or ABA, levels may help determine patient selection for their cancer drug.
Imprime PGG is a yeast-derived, soluble β-glucan that works in conjunction with therapeutic monoclonal antibodies to create the anticancer immune response by binding and priming innate immune cells. Some of these cells include neutrophils, monocytes, and macrophages.1Essentially, Imprime is a treatment designed to enhance the body's natural tumor killer function, primarily known as Natural Killer (NK) cells.2
Biothera researchers have previously focused their studies on the drug’s ability to execute this “anti-cancer” affect on the specific immune system monocytes, macrophages and neutrophils.2In their studies, the Biothera team examined levels of a cell surface marker, LAMP-1, which signals the killing activity in an NK cell. Through this, they discovered that Imprime PGG treatment had enhanced the LAMP-1 “expression on NK cells exposed to cancer cells derived from T cell lymphomas and erthroleukemias.”2
In Biothera’s presentation, researchers further analyzed the company’s drug in relation to ABA levels and found that the binding of neutrophil and monocyte to Imprime PGG was lower in some individuals with high ABA levels.
“These data provide evidence that, in addition to the concentration of ABA in serum, a genetic variant of the IgG receptor, CD32A, is a critical determinant for the binding of the Imprime ABA complex to neutrophils and monocytes,” said Jeremy Graff, PhD, senior vice president, Biothera Pharmaceutical Research, in a statement.1“Importantly, this genetic variant provides a binary, genetic marker that may enhance our ability to select patients most likely to respond to Imprime-based therapy.”
According to the report, Imprime PGG specifically binds to the innate immune effector cells that are involved in the process of creating the naturally forming ABA (IgG). Previous research has already indicated that there is an ABA (IgG) threshold cutoff for when the drug binds with both neutrophils and monocytes.1
The researchers ultimately concluded that the concentration of ABA and the FCGR2A gene play a critical role in the ability for an individual to bind with the Imprime immunotherapy drug. The Biothera team determined that either or both of these factors might alter patient selection to those who are most likely to gain therapeutic benefit from Imprime treatment.3
Various clinical trials involving Imprime PGG have already been completed or are currently in the works, many of which are focused in the hematology, colorectal cancer and non-small cell lung cancer fields. Biothera’s drugs are currently active as Investigational New Drug fillings under the U.S. Food and Drug Administration.4
“These exciting results further enhance our understanding of Imprime PGG’s ability to enlist the full functionality of the innate immune system to orchestrate a coordinated, anti-cancer immune attack,” said Dr Graff in a statement.2
The international conference was jointly sponsored by the Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research.
1.BusinessWire. Biothera reports additional biomarker data for predicting response to its investigational cancer immunotherapy drug. Available at: http://www.businesswire.com/news/home/20150916006187/en/Biothera-Reports-Additional-Biomarker-Data-Predicting-Response#.VgDQjWTBzGd. Accessed September 22, 2015.
2. Biothera.com. Biothera’s Cancer Immunotherapy Drug Imprime PGG Elicits Increased Natural Killer Cell Activation and Cancer Cell Killing | Biothera. 2015. Available at: http://www.biothera.com/biotheras-cancer-immunotherapy-drug-imprime-pgg-elicits-increased-natural-killer-cell-activation-and-cancer-cell-killing/. Accessed September 23, 2015.
3. Biothera. Endogenous anti-β-glucan antibodies and FcgRIIA (CD32a) single nucleotide polymorphisms (SNP) as potential predictive biomarkers for the efficacy of Imprime PGG immunotherapy in cancer patients. Available at: http://www.biothera.com/wp-content/uploads/2015/09/A014-AACR_Sep2015-SNP-Final.pdf. Accessed September 22, 2015.
4. Biothera.com. Clinical Trials | Biothera. 2015. Available at: http://www.biothera.com/pharmaceutical/clinical-trials/. Accessed September 23, 2015.