Avid Bioservices Inc (CDMO)

[cjgaddy]

Learning more about “ACT”, MSKCC+PPHM 4-3-17 AACR’17 #1651

Apr1-5: AACR 2017, WashDC http://tinyurl.com/mxz23gz - SUMMARY of PPHM’s 5 AACR’17 ABSTRACTS:
1. MSKCC+PPHM: 4-2-17/1pm #574, “PSTargeting+RAD+AntiPD1 Promotes Anti-Tumor Activity, Melanoma” (same as SITC'16/11-14-16 http://tinyurl.com/js3fca4 )
2. MSKCC+PPHM: 4-3-17/8am #1651, “PSTargeting+Adoptive TCell Transfer (ACT) Eliminates Adv. Tumors w/o Off-Target Toxicities, Melanoma” <=NEW(2nd) Joint MemSloan/PPHM study
3. PPHM: 4-4-17/8am #3652, “PSTargeting+LAG3+AntiPD1 Significantly Enhances Anti-Tumor Activity, Triple- MBC”
4. IMMUNOVACCINE+PPHM: 4-4-17/8am #3657, ”PSTargeting Enhances Anti-Tumor Activity of a Tumor Vaccine(DepoVax), HPV-Induced Tumor” https://www.imvaccine.com See 3-24-17:
5. PPHM+VANDERBILT+PRECISIONMEDICINE+PROVIDENCECC: 4-3-17/1pm #CT159/25 (Session: Ph2/3 Clinical Trials in Progress), “IFN-y Analysis In Blood & Tissue as a Potential Prognostic and/or Predictive Biomarker” (abstract embargoed, Sunrise Biomarker #3) - See below.
ALSO: Peregrine Exhibiting – booth #3312.

= = = = = = = = = = = = = = = =
AACR’17 PPHM#2: 4-3-17/8am #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS
“Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” <=NEW(2nd) MSK STUDY$$$
=> Daniel Hirschhorn-Cymerman 1, Sara Sara Schad 1, Sadna Budhu 1, Zhong Hong 1, Xia Yang 1, Hutchins T. Jeff 2, Bruce D. Freimark 2, Michael J. Gray 2, Jedd Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]
1=Memorial Sloan Kettering CC, NYC [ http://www.mskcc.org/research-areas/labs/jedd-wolchok ]
2=Peregrine Pharmaceuticals
ABSTRACT:
A viable strategy to treat advanced cancers includes transferring of tumor-specific T cells. T cells that recognize tumor antigens can be expanded and reinvigorated ex-vivo. Furthermore, autologous T cells can be genetically modified to express anti-tumor T cell receptors [TCRs] or chimeric antigen receptors [CARs]. Although the potency and specificity of tumor-specific T cells can be manipulated ex-vivo, once re-infused into patients, the T cells are subjected to immunosuppressive mechanisms established by the tumor. An important immune checkpoint regulator within tumors is phosphatidylserine (PS). Innate immune cells exposed to PS secrete suppressive cytokines and chemokines that can significantly impair the function and activation of anti-tumor T cells. Therefore, monoclonal antibodies that block PS activity can increase the anti-tumor potency of transferred T cells to treat aggressive cancers. Here we show that a PS targeting monoclonal antibody in combination with CD4+ T cells that recognize the melanoma antigen Trp1 can regress very advanced melanomas in all treated mice. Combination of anti-Trp1 CD4+ T cells with other immunomodulatory modalities such as anti-OX40 antibodies, can achieve equivalent treatment rates but these are typically accompanied by severe immune related adverse events. In contrast, in this setting, PS blockadedid not show any off-target toxicities. Flow cytometry analysis revealed lower levels of CD206 expression concomitant with higher activation markers in macrophages and neutrophils in tumors from anti-PS treated mice. These results suggest that diminishing suppressive mechanisms locally in adoptive transfer protocols is a highly desirable strategy that can eliminate tumors while minimizing related adverse events.
----------
NOTE1:
From 3-2014 Immunotherapy article: “Cancer immunotherapy, particularly adoptive cell transfer (ACT), has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to std. Therapies” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372895
NOTE2:
Through the support from SEAN PARKER, Stand Up To Cancer (SU2C) and the Cancer Research Institute (CRI) formed an Immunology Research Dream Team dedicated to cancer immunology: “Immunologic Checkpoint Blockade & Adoptive Cell Transfer in Cancer Therapy.” The Immunotherapy Dream Team is focused on 2 approaches for this translational cancer research project, which will unite laboratory & clinical efforts towards the immunological treatment, control, and prevention of cancer.
The 1st is investigating blockades (by inhibitory molecules called “checkpoints”) of T lymphocytes’ inhibitory receptors, which block immune responses; and the use of antibodies to remove the checkpoints, once again allowing white blood cells called T lymphocytes to kill the cancer cells.
Second, the Immunotherapy Dream Team is pursuing multiple Adoptive Cell Transfer (ACT) approaches, which increase immunity.”
DREAM TEAM LEADERSHIP: 10 scientists, incl. MSKCC’s Jedd D. Wolchok & Michel Sadelain.
http://parker.org/initiatives/immunotherapy
------------------------------
8-2015: Presently there are 3 types of Adoptive Cell Transfer (ACT) using effector T cells that are advancing on a path towards regulatory approval:
1. TILs (tumor infiltrating lymphocytes) have been developed with slow but continuing progress over several decades.
2. CARs (chimeric antibody receptors) – newer gene-modified T cells strategy
3. TCRs (T-cell receptors) – newer gene-modified T cells strategy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507286/

...“Adoptive cell transfer is like ‘giving patients a living drug’,” states Renier J. Brentjens, MD/PhD, of Memorial Sloan Kettering Cancer Center (MSKCC).
… https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
...“Adoptive T cell therapy (ACT) is one stone in this new pillar, a potentially powerful approach to cancer treatment that relies on the infusion of tumor-specific T cells.”
… https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327320
= = = = = = = = =
Interesting 3-31-17 Sloan Kettering Tweet re: AACR’17
3-31-17 9:20amET “Getting ready for #AACR17? #Immunotherapy will be a hot topic. Learn more about how it works (video). @AACR”
https://twitter.com/sloan_kettering
Points to this 4-2016 Video (1:20):
“Immunotherapy – How It Works” https://www.youtube.com/watch?v=COQ1AeoGyco
Beg@:39:
“Immunotherapy drugs release this brake and empower immune cells to fight the cancer.
Sometimes the immune system needs a tune-up before it can fight cancer.
Immune cells can be removed from the body, armed with new proteins that can target cancer cells, and given back to a patient in large numbers.
Once inside the body, the modified immune cells recognize and attack the cancer.
This approach is called CAR T cell therapy. [an Adoptive Cell Transfer “ACT” strategy]
Despite the promise of immunotherapy, not everybody responds.
MSKCC scientists are exploring ways to improve immunotherapy.”

=============AND, THIS 3-23-17 PARKER FOUNDATION RELEASE ON AACR’17:
3-23-17: “Parker Institute for Cancer Immunotherapy Scientists to Present Research on Checkpoint Inhibitors, Adoptive Cell Therapy, and Other Advances in Immuno-oncology at AACR 2017”
Investigators affiliated with the Parker Institute for Cancer Immunotherapy will present some of the most anticipated immuno-oncology research at the 2017 AACR Annual Meeting. The event takes place at the Walter E. Washington Convention Center in Washington, DC, April 1-5 2017. . .
Other adoptive cell therapy abstracts of interest:
• ”Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” [see http://tinyurl.com/nx5q5os ]
The principal investigator is Taha Merghoub, PhD, Parker Institute member researcher at Memorial Sloan Kettering Cancer Center. Co-authors include Parker Institute Center Director Jedd Wolchok, MD, PhD, at Memorial Sloan Kettering Cancer Center.
http://www.parkerici.org/media/2017/parker-institute-for-cancer-immunotherapy-scientists-to-present-research-on

INTERESTING: Mem. Sloan’s Dr. Jedd. Wolchok is co-author of 9 AACR’17 abstracts. 2 of the 9 are w/PPHM re: PS-Targeting. With biotechs, he has one each with Genocea Biosciences(ex-vivo screening), Infinity Pharm(Ph1), Leap Ther.(Ph1), and two with BMS(Ph1+Ph3). The 8th is MSKCC ONLY, and the 9th is jointly w/Cedars-Sinai/LA. http://www.abstractsonline.com/pp8/#!/4292 .
PEREGRINE (Joint Mem.Sloan Kettering Wolchok Lab & PPHM):
1. 4-2-17 #574 “Phosphatidylserine Targeting Antibody in Combination with Tumor Radiation & Immune Checkpoint Blockade Promotes Anti-Tumor Activity in Mouse B16 Melanoma” <=Same as SITC’16 11-14-16.
4-3-17 #1651 “Targeting Phosphatidylserine in Combination With Adoptive T Cell Transfer Eliminates Advanced Tumors Without Off-Target Toxicities in a Melanoma Preclin. Model” <=NEW/2nd PPHM+MSK.
NON-PEREGRINE:
3. (MSK ONLY): 4-2-17 #874 “Lifting the iron curtain: Imaging cellular barriers to combination chelation-immune checkpoint therapy”
4. (MSK & Genocea Bio. http://www.genocea.com GNCA/$130mm MktCap) 4-2-17 #632 “Genome-scale neoantigen screening using ATLAS prioritizes candidate antigens for immunotherapy in a NSCLC patient”
5. (MSK & Cedars-Sinai/LA) 4-4-17 #4705 “CTLA4 blockade with HER2-directed therapy yields clinical benefit in women undergoing radiation therapy for HER2+ breast cancer brain metastases”
6. (MSK & Infinity Pharm.) 4-4-17 #CT089 “A Ph1, first-in-human study of IPI-549, a PI3K-y inhibitor, as monotherapy & in combo w/nivolumab in adv. solid tumors”
7. (MSK & Leap Ther.) 4-2-17 #CT018 “Intratumor & peripheral Treg modulation as a pharmacodynamic biomarker of the GITR agonist antibody TRX-518 in the 1st in-human trial”
8. (MSK & BMS) 4-3-17 #CT073 “(Ph1) Immunomodulatory effects of NIVO+IPI or NIVO/mono in adv. melanoma: CheckMate038”
9. (MSK & BMS) 4-3-17 #CT075 “OS results from a Ph3 of NIVO+IPI in treatment-naïve pts w/adv. Melanoma: CheckMate067”