mAbXcite: a novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils
The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that are immune active.I...
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Published in | Journal for immunotherapy of cancer Vol. 2; no. S3; p. P262 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
BMJ Publishing Group LTD
06.11.2014
BioMed Central Ltd BioMed Central |
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Abstract | The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that are immune active.Immune cells that have not received as much attention in cancer immunotherapy are neutrophils. Neutrophils are the most abundant white blood cells, which protect us from microbial infections. They are the first line of innate defense: they arrive early on in the course of infection, phagocytose, and release the content of their granules, including reactive oxygen species and enzymes. Neutrophils also communicate with other immune cells, such as macrophages, dendritic cells, and T cells, by releasing cytokines and chemokines.There has long been a call to recruit these professional killers to fight cancer. However, an approach that mediates the recruitment of neutrophils has to lead to acute as opposed to chronic inflammation to overcome the suppressive environment that tumors surround themselves with.We have developed a novel immunotherapy platform technology, termed mAbXcite, which directs and activates neutrophils to kill cancer cells in a targeted manner. The targeting is achieved by using monoclonal antibodies that are chemically linked to beta-1,6-glucan, a saccharide found on the cell walls of fungal species which recruits and activates neutrophils. The resulting mAb construct attracts mediators of acute inflammation, notably neutrophils, leading to rapid destruction of cancer cells.We will present proof-of concept of the mAbXcite technology using two validated antibodies, the anti-Her2 Trastuzumab and the anti-EGFR Cetuximab. In preclinical xenograft models, these mAbXcite constructs demonstrate significantly greater efficacy than the original antibody in resistant tumor models. Furthermore, some mice show complete regressions and do not grow tumors upon rechallenge, suggesting a long term immune response. We will also provide pharmacodynamics results, primarily neutrophil infiltration by histology and live imaging, as well as pharmacokinetics results, demonstrating that the linked oligosaccharide is stable and is not affecting the half-life of the antibodies.This novel immunotherapy platform is suitable for peripheral membrane targets that are overexpressed on tumors, and does not require antibody internalization. The unique mechanism of action of recruiting and activating neutrophils against cancer could be synergistic with other immunotherapeutic approaches. |
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AbstractList | The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that are immune active.Immune cells that have not received as much attention in cancer immunotherapy are neutrophils. Neutrophils are the most abundant white blood cells, which protect us from microbial infections. They are the first line of innate defense: they arrive early on in the course of infection, phagocytose, and release the content of their granules, including reactive oxygen species and enzymes. Neutrophils also communicate with other immune cells, such as macrophages, dendritic cells, and T cells, by releasing cytokines and chemokines.There has long been a call to recruit these professional killers to fight cancer. However, an approach that mediates the recruitment of neutrophils has to lead to acute as opposed to chronic inflammation to overcome the suppressive environment that tumors surround themselves with.We have developed a novel immunotherapy platform technology, termed mAbXcite, which directs and activates neutrophils to kill cancer cells in a targeted manner. The targeting is achieved by using monoclonal antibodies that are chemically linked to beta-1,6-glucan, a saccharide found on the cell walls of fungal species which recruits and activates neutrophils. The resulting mAb construct attracts mediators of acute inflammation, notably neutrophils, leading to rapid destruction of cancer cells.We will present proof-of concept of the mAbXcite technology using two validated antibodies, the anti-Her2 Trastuzumab and the anti-EGFR Cetuximab. In preclinical xenograft models, these mAbXcite constructs demonstrate significantly greater efficacy than the original antibody in resistant tumor models. Furthermore, some mice show complete regressions and do not grow tumors upon rechallenge, suggesting a long term immune response. We will also provide pharmacodynamics results, primarily neutrophil infiltration by histology and live imaging, as well as pharmacokinetics results, demonstrating that the linked oligosaccharide is stable and is not affecting the half-life of the antibodies.This novel immunotherapy platform is suitable for peripheral membrane targets that are overexpressed on tumors, and does not require antibody internalization. The unique mechanism of action of recruiting and activating neutrophils against cancer could be synergistic with other immunotherapeutic approaches. |
ArticleNumber | P262 |
Author | Siedlecki, James Carlson, Mark Miao, Hua Rubin-Bejerano, Ifat Reznik, Gabriel Kane, John Sansal-Castellano, Isabelle Dostalova, Zuzana |
AuthorAffiliation | 1 ImmuneXcite Inc., USA |
AuthorAffiliation_xml | – name: 1 ImmuneXcite Inc., USA |
Author_xml | – sequence: 1 givenname: Ifat surname: Rubin-Bejerano fullname: Rubin-Bejerano, Ifat – sequence: 2 givenname: Isabelle surname: Sansal-Castellano fullname: Sansal-Castellano, Isabelle – sequence: 3 givenname: Mark surname: Carlson fullname: Carlson, Mark – sequence: 4 givenname: Gabriel surname: Reznik fullname: Reznik, Gabriel – sequence: 5 givenname: James surname: Siedlecki fullname: Siedlecki, James – sequence: 6 givenname: John surname: Kane fullname: Kane, John – sequence: 7 givenname: Zuzana surname: Dostalova fullname: Dostalova, Zuzana – sequence: 8 givenname: Hua surname: Miao fullname: Miao, Hua |
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Copyright | 2014 Rubin-Bejerano et al.; licensee BioMed Central Ltd This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. Copyright © 2014 Rubin-Bejerano et al.; licensee BioMed Central Ltd. 2014 Rubin-Bejerano et al.; licensee BioMed Central Ltd. |
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SubjectTerms | Antibodies Cancer Immunotherapy Monoclonal antibodies Neutrophils Poster Presentation Tumors |
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Title | mAbXcite: a novel immunotherapy platform that initiates a robust anti-cancer immune response by recruiting and activating neutrophils |
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