AI
Sunday, February 12, 2017 10:33:54 AM
Preclin. Anti-PS work w/collab’s MemSloan,Duke,MDA,Rutgers,Wistar,ImmunoVaccine…
AACR’17: 4-3-17 #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS http://tinyurl.com/z47hb2s
MemSloan Jedd Wolchok Lab+PPHM(2nd known study): “Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model”
Lead author: Dr. Taha Merghoub (Co-Dir., Ludwig Collaborative Lab at MSK), Co-author Jedd Wolchok, PPHM & MSKCC scientists. ( http://www.mskcc.org/research-areas/labs/jedd-wolchok )
NOTE:
“Adoptive Cell Transfer (ACT)” is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system, with the goal of improving immune functionality and characteristics. In cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. AACR’17: http://tinyurl.com/jxfm3hb
AACR’17: 4-4-17 #3657 - Session: BITES BISPECIFICS & CHECKPOINTS
”Phosphatidylserine-Targeting Antibodies Enhance Anti-Tumor Activity of a Tumor Vaccine in a HPV-Induced Tumor Model”
=> Genevieve Weir 1, Tara Quinton 1, Jeff Hutchins 2, Bruce Freimark 2, Marianne Stanford (VP/Res., Immunovaccine Inc.)
1=Immunovaccine, Inc., Halifax, NS, Canada [ https://www.imvaccine.com ]; 2=Peregrine Pharmaceuticals
[Note: POSSIBLE GENESIS OF IMMUNOVACCINE COLLAB??? 11-9-15 SITC'15: ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.” http://tinyurl.com/pbof95w ]
BAVI MOA: 2-9-17/AACR article (Rutgers’ Dr. Raymond Birge, PPHM, Advanced Proteome Therapeutics, etal): “PS Sensing by TAM Receptors (Tyro3, Axl, Mertk)...” http://tinyurl.com/gna9q4v
…”These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1 based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to up-regulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on breast cancers cells.”
BAVI MOA: 1-30-17 Mol.Cancer article: MDA/UTSW/Brekken/etal, “PreClin. Eval of DNX2401+FhuBAVI(1N11) for Pancreatic Cancer” http://tinyurl.com/hov4hfb
...Combo Delta-24-RGD + FhuBAVI “significantly inhibited tumor growth; further enhanced its anticancer activity; warrants further clinical evaluation...”
BAVI MOA 11-14-16: SITC’16: Joint Memorial Sloan Kettering (Wolchok Lab) & PPHM poster on Triple Combo Rad+Bavi+aPD1 vs. Melanoma http://tinyurl.com/js3fca4
...MSK’s Dr. Jedd Wolchok states, ”Based on these study results, we believe that the targeting of PS is having meaningful activity within the tumor microenvironment in the B16 melanoma model. It appears that this activity creates a more immune active environment in which other treatments, including radiation, are able to have a greater anti-tumor impact."
BAVI MOA 10-22-16: Duke’s Herbert K. Lyerly (w/PPHM) poster on AntiPS/TNBC data at AACR’s Tumor Immunotherapy Conf./Boston http://tinyurl.com/zzryfok
...”Title: ‘Modulating The Tumor Microenvironment to Enhance Cancer Immunotherapy by Inducing Phosphatidylserine Expression on the Tumor Surface”’… Data showed that a combination of anti-PS & anti-PD-L1 therapies, with or without paclitaxel, led to greater anti-tumor responses than any of the treatments administered as single agents or dual treatment combinations w/paclitaxel, in the E0771 murine model of TNBC.”
BAVI MOA 9-27-16 AACR-CRI/Dr. Michael Gray (PPHM): Preclin. Triple-Combo Bavi+PD1+LAG3 TNBC data in TNBC (80% Compl. Regression, Stat-Sig. Incr. in Key Tumor Fighting Immune Cells) http://tinyurl.com/zy9yv78
BAVI MOA 7-27-16 Shaul/Brekken/Thorpe/etal PLOS ONE article: Fhu/Bavi vs. APS-related Pregnancy Complications & Thrombosis http://tinyurl.com/jlhrdg2
...”The potential clinical impact of 1N11 (Fhu Bavi) in patients with APS is substantial. Spring-boarding from the present discovery of 1N11 as a highly-effective, mechanism-based treatment for APS in a comprehensive series of mouse models of APS-related disorders, clinical studies of 1N11 now warrant consideration.”
BAVI MOA 5-11-16 Breast Cancer Res. article, B.Freimark/CW.Hughes(UCal-Irvine)-et-al, “PS-Targeting/Bavi Combo w/Anti-PD1/PDL1 in Triple.Neg-MBC” http://tinyurl.com/zxu882y
...”our observations demonstrate that including PS-targeting antibodies such as bavituximab can enhance the anti-tumor activity of anti-PD-1/PD-L1 treatments, not only by increasing TIL responses but also by inhibiting cytokines stimulated by single-agent anti-PD-1 therapy that serve to suppress the immune response & promote tumor progression.”
BAVI MOA 4-20-16/AACR'16 & 4-4-16/Cancer-Immunology-Res.(AACR) article (PPHM/Friemark, U.Cal-Irvine/CW-Hughes - preclin. data: Bavi combo w/anti-PD-1/anti-CTLA-4 “induces a shift in tumor microenvironment from immunosuppressive to immune active” http://tinyurl.com/jyox458
BAVI MOA 1-18-16: CEO Steve King explains PPHM's direct PS-Targeting advantage vs. the “individual-receptors” PS-binding approach of others like: Axl Mer TIM-3 RAGE Tyro3 GAS6 CD300a BAI1 MFG-E8 etc. http://tinyurl.com/h2h87mc
2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, ”Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9
11-9-15 SITC'15: New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w
...Also, collab. with Dr. Bernard Fox (Immunotherapist/Earle A. Chiles Res.Inst.) on new Immuno-Profiling Clinical Test (Opal 6-plex quantitative IF Assay), PPHM roundtable with Raymond Birge (Rutgers), Douglas Graham (Emory), Dmitry Gabrilovich (Wistar), Rolf Brekken (UTSW), Maria Karasarides (AstraZeneca) - ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.”
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8
...Dr. Wolchok states, ”The phosphatidylserine (PS) signaling pathway is a very interesting target for modulating the immune system's response to cancer. We look forward to exploring the potential of PS-targeting agents alone and with other immune modulators that may lead to novel advances in cancer therapy.”
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AACR’17: 4-3-17 #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS http://tinyurl.com/z47hb2s
MemSloan Jedd Wolchok Lab+PPHM(2nd known study): “Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model”
Lead author: Dr. Taha Merghoub (Co-Dir., Ludwig Collaborative Lab at MSK), Co-author Jedd Wolchok, PPHM & MSKCC scientists. ( http://www.mskcc.org/research-areas/labs/jedd-wolchok )
NOTE:
“Adoptive Cell Transfer (ACT)” is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system, with the goal of improving immune functionality and characteristics. In cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. AACR’17: http://tinyurl.com/jxfm3hb
AACR’17: 4-4-17 #3657 - Session: BITES BISPECIFICS & CHECKPOINTS
”Phosphatidylserine-Targeting Antibodies Enhance Anti-Tumor Activity of a Tumor Vaccine in a HPV-Induced Tumor Model”
=> Genevieve Weir 1, Tara Quinton 1, Jeff Hutchins 2, Bruce Freimark 2, Marianne Stanford (VP/Res., Immunovaccine Inc.)
1=Immunovaccine, Inc., Halifax, NS, Canada [ https://www.imvaccine.com ]; 2=Peregrine Pharmaceuticals
[Note: POSSIBLE GENESIS OF IMMUNOVACCINE COLLAB??? 11-9-15 SITC'15: ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.” http://tinyurl.com/pbof95w ]
BAVI MOA: 2-9-17/AACR article (Rutgers’ Dr. Raymond Birge, PPHM, Advanced Proteome Therapeutics, etal): “PS Sensing by TAM Receptors (Tyro3, Axl, Mertk)...” http://tinyurl.com/gna9q4v
…”These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1 based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to up-regulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on breast cancers cells.”
BAVI MOA: 1-30-17 Mol.Cancer article: MDA/UTSW/Brekken/etal, “PreClin. Eval of DNX2401+FhuBAVI(1N11) for Pancreatic Cancer” http://tinyurl.com/hov4hfb
...Combo Delta-24-RGD + FhuBAVI “significantly inhibited tumor growth; further enhanced its anticancer activity; warrants further clinical evaluation...”
BAVI MOA 11-14-16: SITC’16: Joint Memorial Sloan Kettering (Wolchok Lab) & PPHM poster on Triple Combo Rad+Bavi+aPD1 vs. Melanoma http://tinyurl.com/js3fca4
...MSK’s Dr. Jedd Wolchok states, ”Based on these study results, we believe that the targeting of PS is having meaningful activity within the tumor microenvironment in the B16 melanoma model. It appears that this activity creates a more immune active environment in which other treatments, including radiation, are able to have a greater anti-tumor impact."
BAVI MOA 10-22-16: Duke’s Herbert K. Lyerly (w/PPHM) poster on AntiPS/TNBC data at AACR’s Tumor Immunotherapy Conf./Boston http://tinyurl.com/zzryfok
...”Title: ‘Modulating The Tumor Microenvironment to Enhance Cancer Immunotherapy by Inducing Phosphatidylserine Expression on the Tumor Surface”’… Data showed that a combination of anti-PS & anti-PD-L1 therapies, with or without paclitaxel, led to greater anti-tumor responses than any of the treatments administered as single agents or dual treatment combinations w/paclitaxel, in the E0771 murine model of TNBC.”
BAVI MOA 9-27-16 AACR-CRI/Dr. Michael Gray (PPHM): Preclin. Triple-Combo Bavi+PD1+LAG3 TNBC data in TNBC (80% Compl. Regression, Stat-Sig. Incr. in Key Tumor Fighting Immune Cells) http://tinyurl.com/zy9yv78
BAVI MOA 7-27-16 Shaul/Brekken/Thorpe/etal PLOS ONE article: Fhu/Bavi vs. APS-related Pregnancy Complications & Thrombosis http://tinyurl.com/jlhrdg2
...”The potential clinical impact of 1N11 (Fhu Bavi) in patients with APS is substantial. Spring-boarding from the present discovery of 1N11 as a highly-effective, mechanism-based treatment for APS in a comprehensive series of mouse models of APS-related disorders, clinical studies of 1N11 now warrant consideration.”
BAVI MOA 5-11-16 Breast Cancer Res. article, B.Freimark/CW.Hughes(UCal-Irvine)-et-al, “PS-Targeting/Bavi Combo w/Anti-PD1/PDL1 in Triple.Neg-MBC” http://tinyurl.com/zxu882y
...”our observations demonstrate that including PS-targeting antibodies such as bavituximab can enhance the anti-tumor activity of anti-PD-1/PD-L1 treatments, not only by increasing TIL responses but also by inhibiting cytokines stimulated by single-agent anti-PD-1 therapy that serve to suppress the immune response & promote tumor progression.”
BAVI MOA 4-20-16/AACR'16 & 4-4-16/Cancer-Immunology-Res.(AACR) article (PPHM/Friemark, U.Cal-Irvine/CW-Hughes - preclin. data: Bavi combo w/anti-PD-1/anti-CTLA-4 “induces a shift in tumor microenvironment from immunosuppressive to immune active” http://tinyurl.com/jyox458
BAVI MOA 1-18-16: CEO Steve King explains PPHM's direct PS-Targeting advantage vs. the “individual-receptors” PS-binding approach of others like: Axl Mer TIM-3 RAGE Tyro3 GAS6 CD300a BAI1 MFG-E8 etc. http://tinyurl.com/h2h87mc
2-2016: Rutgers' Dr. Raymond Birge's relationship with Peregrine & UTSW's Dr. Rolf Brekken and his 2-26-16 article, ”Phosphatidylserine is a Global Immunosuppressive Signal in Efferocytosis, Infectious Disease, and Cancer” http://tinyurl.com/z5d9qt9
11-9-15 SITC'15: New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w
...Also, collab. with Dr. Bernard Fox (Immunotherapist/Earle A. Chiles Res.Inst.) on new Immuno-Profiling Clinical Test (Opal 6-plex quantitative IF Assay), PPHM roundtable with Raymond Birge (Rutgers), Douglas Graham (Emory), Dmitry Gabrilovich (Wistar), Rolf Brekken (UTSW), Maria Karasarides (AstraZeneca) - ”Combining Bavi w/anti-PD-1 significantly enhanced O/S… significant incr. CD45+, CD8+ and CD3+ T-cells… led a prolonged anti-tumor immune response which protected the animals against a re-challenge w/same tumor.”
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/o3k9ux8
...Dr. Wolchok states, ”The phosphatidylserine (PS) signaling pathway is a very interesting target for modulating the immune system's response to cancer. We look forward to exploring the potential of PS-targeting agents alone and with other immune modulators that may lead to novel advances in cancer therapy.”
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