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Burlingame, CA, United States

Chapuis A.G.,Fred Hutchinson Cancer Research Center | Ragnarsson G.B.,Fred Hutchinson Cancer Research Center | Nguyen H.N.,Fred Hutchinson Cancer Research Center | Chaney C.N.,Fred Hutchinson Cancer Research Center | And 19 more authors.
Science Translational Medicine | Year: 2013

Relapse remains a leading cause of death after allogeneic hematopoietic cell transplantation (HCT) for patients with high-risk leukemias. The potentially beneficial donor T cell-mediated graft-versus-leukemia (GVL) effect is often mitigated by concurrent graft-versus-host disease (GVHD). Providing T cells that can selectively target Wilms tumor antigen 1 (WT1), a transcription factor overexpressed in leukemias that contributes to the malignant phenotype, represents an opportunity to promote antileukemic activity without inducing GVHD. HLA-A&z.ast;0201-restricted WT1-specific donor-derived CD8+ cytotoxic T cell (CTL) clones were administered after HCT to 11 relapsed or high-risk leukemia patients without evidence of on-target toxicity. The last four treated patients received CTL clones generated with exposure to interleukin-21 (IL-21) to prolong in vivo CTL survival, because IL-21 can limit terminal differentiation of antigen-specific T cells generated in vitro. Transferred cells exhibited direct evidence of antileukemic activity in two patients: a transient response in one patient with advanced progressive disease and the induction of a prolonged remission in a patient with minimal residual disease (MRD). Additionally, three treated patients at high risk for relapse after HCT survive without leukemia relapse, GVHD, or additional antileukemic treatment. CTLs generated in the presence of IL-21, which were transferred in these latter three patients and the patient with MRD, all remained detectable long term and maintained or acquired in vivo phenotypic and functional characteristics associated with long-lived memory CD8+ T cells. This study supports expanding efforts to immunologically target WT1 and provides insights into the requirements necessary to establish potent persistent T cell responses. Copyright 2013 by the American Association for the Advancement of Science; all rights reserved. Source


Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.


Patent
Igenica Inc. | Date: 2014-06-06

Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 215.74K | Year: 2014

DESCRIPTION (provided by applicant): Antibody drug conjugates (ADCs), a rapidly growing class of targeted therapeutics, represent a promising new approach toward improving both the selectivity and the cytotoxic activity of cancer drugs. Although several ADCs have demonstrated recent clinical success, the utility of most ADCs currently in development is limited by cumbersome synthetic processes, insufficient anti-tumor activity, and unpredictable toxicity. We believe that these drawbacks can be addressed byimprovements in both linker technology and the cytotoxic drugs used to construct the ADCs. Our broad long-term goal is to develop novel ADCs with improved potency, homogeneity and stability over existing targeted therapeutics. Igenica has developed two proprietary technology platforms that provide a complementary function-oriented screening strategy to systematically identify novel tumor associated antigen targets and antigen-specific monoclonal antibodies for constructing ADCs with improved pharmacolo


BURLINGAME, Calif.--(BUSINESS WIRE)--Igenica Biotherapeutics, Inc., a company focused on the discovery and development of innovative antibody-based therapies for the treatment of cancer, announced today that it has entered into an oncology research agreement with MedImmune, the global biologics research and development arm of AstraZeneca (NYSE: AZN). Igenica and MedImmune will evaluate the potential of antibody-drug conjugates (ADCs) targeting Surface Antigen in Leukemia (SAIL), a novel cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Preclinical data have supported the selective targeting of tumors expressing SAIL with ADCs. Under the agreement, Igenica will contribute its proprietary anti-SAIL antibodies, including IGN786, and its proprietary SNAP ADC drug linker, and MedImmune will provide its proprietary anti-tumor payload. Igenica and MedImmune will then jointly investigate the resulting novel ADC in preclinical studies. MedImmune will receive an option to an exclusive worldwide license to anti-SAIL antibodies and antibody-drug conjugates resulting from the collaboration. Igenica will receive an exclusive option fee and, if MedImmune exercises its option, is also eligible to receive an upfront license fee, clinical, regulatory and commercialization milestones, and royalties on net sales. MedImmune will fund all development and commercialization costs under a license agreement. “We are pleased to collaborate with MedImmune, a leading biotechnology company, to build on our pioneering research,” commented John Celebi, Chief Business Officer, Igenica. “This agreement provides a strong opportunity to realize the potential value of IGN786 and complements our strategy focused on targeting drugs to block the immunosuppressive activities of immune cells in the tumor microenvironment to reinvigorate or activate de novo anti-tumor responses.” “We look forward to working with Igenica Biotherapeutics on developing a novel antibody-drug conjugate in hematology,” said Ronald Herbst, Vice President, Oncology Research & Development, MedImmune. “Developing next generation antibody-drug conjugates is a key strategic area for us, and we are committed to advancing our pipeline in this area both externally and internally.” IGN786 is a humanized monoclonal antibody that binds to SAIL, a cell surface protein with high prevalence of expression in a variety of hematologic malignancies and several solid tumors. Igenica was the first to describe the biological properties of human SAIL and elucidate its potential as an antibody-drug conjugate approach (Blood Cancer Journal (2015) 5, e316). Preclinical data with IGN786 have supported the selective targeting of tumors expressing SAIL with antibody-drug conjugates. Igenica Biotherapeutics is focused on the discovery of innovative antibody-based therapies for the treatment of cancer. Igenica’s integrated discovery engine has generated a novel pipeline of immunotherapies and ADCs that address the critical needs of cancer patients. Igenica is funded by a premier group of life science investors including The Column Group, OrbiMed, 5AM Ventures and Third Rock Ventures. For more information, please visit www.igenica.com. Guggenheim Partners, LLC served as an advisor to Igenica on the transaction.

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