On November 12, 2021 CERo Therapeutics, Inc., a biopharmaceutical company pioneering the development of novel autologous engineered immune cell therapies, reported the results from preclinical in vitro studies describing the characterization of novel chimeric engulfment receptor (CER) T cells (Press release, Cero Therapeutics, NOV 12, 2021, View Source [SID1234595466]). CERs are genetically engineered proteins that bind to tumor-agnostic, inducible stress ligands on the surface of tumor cells to provoke tumor-specific cytotoxicity and innate immune functions such as engulfment and antigen presentation. The data, which are being presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), demonstrate that T cells engineered to express CERs exhibit multifunctional properties of both innate and adaptive immune responses and suggest the potential for CER T cells to overcome barriers associated with existing adoptive cell-based therapies.

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"These studies highlight for the first time the unique orthogonal profile of CER T cells to combine the tumor cell clearance attributes of macrophages and dendritic cells of the innate immune system with the T-cell activation of the adoptive immune system into a single engineered T cell," said Daniel Corey, MD, founder and CEO of CERo. "One of the limitations of activated T cells is their poor ability to present antigens due to inefficient antigen capture. In contrast, CER T cells facilitate antigen capture, processing and presentation, and impart target-dependent cytokine function, thereby offering a possible means of improving the therapeutic potential of engineered cell therapies."

In the studies, CER T cell constructs containing an extracellular phagocytic receptor were characterized for multiple functions, including cytotoxicity in combination with a Bruton’s tyrosine kinase inhibitor (BTKi), tumor cell fragment uptake, T-cell activation, cytokine induction, and antigen-presenting cell (APC)-like activity. Results of these in vitro studies showed that CER T cells synergized with a BTKi to enhance killing of a mantle cell lymphoma tumor cell line. Further, CER T cells exhibited abilities to capture tumor cell fragments and induce expression of T-cell activation markers and cytokines. CER T cells containing a toll-like receptor (TLR) domain also showed enhanced ability to present exogenous antigen and activate antigen-specific TCR T cells.

The poster entitled "Enhanced antigen capture, antigen-presenting cell (APC)-like function, and cytotoxic responses with chimeric engulfment receptor (CER) T cells" (Abstract #207) is now accessible virtually via the SITC (Free SITC Whitepaper) website and in person today from 7:00 a.m. – 8:30 p.m. ET in Exhibit Hall E.

About CERo’s Platform Technology

CERo’s technology aims to expand the therapeutic potential of engineered T cell-based therapies by introducing distinct and complementary tumor cell clearance pathways into a single T cell. By engineering T cells to express CERs, CERo’s platform technology enables T cells to target tumors, induce cellular damage, engulf tumor fragments, and clear tumors, effectively harnessing the anti-tumor attributes of both innate and adaptive immune responses. CER T-cell products are designed to generate a more complete and durable anti-tumor response. This novel biology amends itself to combinations with classic CAR T-cell or small molecule therapy and has potential applications in hematologic malignancies and solid tumors.

On November 12, 2021 Carisma Therapeutics Inc., a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported for the first time preliminary findings from the landmark Phase 1 multi-center clinical trial of CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) (Press release, Carisma Therapeutics, NOV 12, 2021, View Source [SID1234595482]).

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The early data were presented by Dr. Kim A. Reiss, MD, Principial Investigator for Carisma’s clinical trial of CT-0508 at the Abramson Cancer Center of the University of Pennsylvania (Penn), at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting. The preliminary findings represent the first clinical data with genetically engineered macrophages in humans and demonstrated that CT-0508 was well tolerated after infusion and there were no dose limiting toxicities. CT-0508 was also successfully manufactured using macrophages obtained from heavily pre-treated, advanced solid tumor patients and showed high CAR expression, viability, and purity. The data also demonstrated that CT-0508 remodeled the solid tumor microenvironment (TME) and mediated expansion/activation of T cells within the tumors. The Food and Drug Administration recently granted Fast Track designation to CT-0508 for the treatment of patients with solid tumors.

"This is the first time that genetically engineered macrophages are being studied in humans and we are encouraged by the safety profile and activity observed thus far," said Debora Barton, MD, Chief Medical Officer at Carisma Therapeutics. "We will continue to enroll patients in the landmark clinical trial of CT-0508 and look forward to making additional observations about how CAR-M therapy can potentially address the unmet needs of patients."

Carisma data also accepted for presentation at the SITC (Free SITC Whitepaper) 36th Anniversary Annual Meeting:

"Chimeric Antigen Receptor Macrophages (CAR-M) Elicit a Systemic Anti-Tumor Immune Response and Synergize with PD1 Blockade in Immunocompetent Mouse Models of HER2+ Solid Tumors," Friday, November 12 at 7:00 am ET
"Development and Characterization of CAR-Mono, a Novel Cell Therapy Platform for Solid Tumor Immunotherapy," Saturday, November 13 at 7:00 am ET
"SIRP⍺ Deficient CAR-Macrophages Exhibit Enhanced Anti-Tumor Function and Bypass the CD47 Immune Checkpoint," Saturday, November 13 at 7:00 am ET
"We are excited by the early Phase I clinical data demonstrating safety, feasibility, and TME remodeling with CT-0508," shared Michael Klichinsky, PharmD, PhD, co-inventor of the CAR-M technology and scientific co-founder and Senior Vice President of Research at Carisma Therapeutics. "Our research team is committed to innovation in the field of genetically modified myeloid cells, and we are excited to also share novel pre-clinical data with CRISPR editing, combination therapy, and manufacturing advances at the upcoming SITC (Free SITC Whitepaper) meeting."

Presentation and posters will be available on the SITC (Free SITC Whitepaper) 36th Anniversary Annual Meeting portal for registered attendees.

Editor’s Note: Dr. Saar Gill and Penn are both co-founders of Carisma and hold equity in the company. Carisma has licensed certain Penn-owned intellectual property from the University, and Penn’s Perelman School of Medicine receives sponsored research funding from the company in support of Dr. Gill’s laboratory and clinical trials at Penn, including the trial led by Dr. Reiss. Penn and Dr. Gill may be entitled to receive future financial benefits from development and commercialization of technologies licensed and optioned to Carisma.

On November 12, 2021 Nordic Nanovector ASA (OSE: NANOV) reported that it will report its results for the third quarter 2021 on Thursday, 18 November 2021 (Press release, Nordic Nanovector, NOV 12, 2021, prnewswire.com/news-releases/nordic-nanovector-asa-invitation-to-third-quarter-2021-results-presentation-and-webcast-301422901.html [SID1234595498]).

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A presentation by Nordic Nanovector’s senior management team will be held in-person and webcast live beginning at 8:30am CET.

The webcast can be accessed from www.nordicnanovector.com in the section: Investors & Media and a recording will also be available on this page after the event.

The results report and the presentation will be available at www.nordicnanovector.com in the section: Investors & Media/Reports and Presentation/Interim Reports/2021 from 7:00am CET the same day.

On November 12, 2021 Alligator Bioscience AB ("Alligator" or the "Company") reported that data highlighting the efficacy and safety of Neo-X-Prime bsAbs and how Alligator’s lead compound targeting CD40 and CEA meets key needs in Immuno-oncology, will be presented at the Society for Immunotherapy Cancer’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting & Pre-Conference Programs virtually on November 10th – 14th, 2021 (Press release, Alligator Bioscience, NOV 12, 2021, View Source [SID1234595322]).

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"We are very excited by this data as it reinforces the robust potential of our proprietary Neo-X-Prime platform. The data shows that simultaneous CD40 engagement and delivery of neoantigen-containing tumor exosomes to antigen-presenting cells mediates an expansion of the tumor-specific T cell repertoire, resulting in potent anti-tumor effects," stated Karin Hagerbrand, PhD., Senior Scientist at Alligator Bioscience. "This is another step forward in the development of our platform technology and we are enthusiastic over the data presented on our lead Neo-X- Prime compound, targeting CD40 and CEA."

Session: Poster Hall

Title: Neo-X-Prime bispecific antibodies targeting CD40 and tumor antigens promote cross-presentation of tumor exosome-derived neoantigen and induce superior anti-tumor responses compared to CD40 mAb

Presenter: Karin Hagerbrand, PhD.

The above poster presentation will be available online at www. View Source on Saturday, November 13, 2021.

On November 12, 2021 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported the presentation of four preclinical data abstracts focused on its natural killer cell platform and pipeline at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36TH Annual Meeting and Pre-Conference Programs (Press release, Nkarta, NOV 12, 2021, View Source [SID1234595340]).

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"The data we presented at this year’s SITC (Free SITC Whitepaper) meeting showcase the rapid and continuous advancement of our NK cell platform and its potential to deliver pioneering off-the-shelf cell therapies," noted James Trager, PhD, Chief Scientific Officer of Nkarta. "Nkarta’s ongoing research activities are designed to heighten the innate ability of NK cells to identify and kill tumor cells and to further build on our efficient and robust manufacturing process. Our findings reported at SITC (Free SITC Whitepaper) support further exploration of CISH gene-knockout CD70 CAR NK cells for clinical application, one focus of our ongoing collaboration with our partners at CRISPR Therapeutics."

Details of the preclinical poster presentations at SITC (Free SITC Whitepaper) follow. Each poster will be available for download shortly after the presentation at View Source

Title: A Combined Strategy of CD70 CAR Co-expression with Membrane-bound IL-15 and CISH Knockout Results in Enhanced NK Cytotoxicity and Persistence*
Abstract Number and Type:16439, oral
Poster Presentation Date and Time: November 10, 2021, 2:40 p.m. ET
This study illustrates multiple approaches to modify NK cells to target CD70, an antigen highly expressed in hematological malignancies and solid tumors, including renal cell carcinoma. Optimal CD70 chimeric antigen receptor (CAR) candidates were identified using high throughput screening approaches. Preclinical results showed that a combined editing and engineering strategy to armor primary NK cells via co-expression of the CD70 CAR and a membrane bound form of IL-15 (mbIL-15), together with knockout of CISH and CD70 genes using the CRISPR/Cas9 system enhanced the persistence in culture and the cytotoxicity of the cells against multiple tumor cell lines. The knockout of CISH also supported the resistance of primary NK cells to suppressive elements active in the tumor microenvironment.

Title: CISH Gene-knockout Anti-CD70-CAR NK Cells Demonstrate Potent Anti-tumor Activity Against Solid Tumor Cell Lines and Provide Partial Resistance to Tumor Microenvironment Inhibition*
Abstract Number and Type: 113, poster
Poster Presentation Date and Time:November 12, 2021, 7:00 am – 8:30 pm ET
Primary NK cells engineered with CD70 chimeric antigen receptor (CAR), membrane bound form of IL-15 (mbIL-15) and knockout of CISH and CD70 genes using the CRISPR/Cas9 system could be produced efficiently, demonstrating consistent knockout and transduction efficiency across donors. Memory like NK cell differentiation of the gene edited NK cells was achieved using a modified K562 stimulatory cell line expressing membrane-bound IL-15 and 4-1BBL with the addition of IL-12 and IL-18 during expansion. Various gene editing candidates were assessed; the knockout of CISH in particular enhanced not only tumor cell killing by CD70 CAR NK cells, but also their persistence in culture and resistance to suppressive molecules associated with the tumor microenvironment, such as TGFß and adenosine.

Title: Potentiating the Large-Scale Expansion and Engineering of Peripheral Blood-Derived CAR NK Cells for Off-the-Shelf Application
Abstract Number and Type: 151, poster
Poster Presentation Date and Time:November 12, 2021, 7:00 am – 8:30 pm ET
The study highlights novel methods for scaling the expansion of engineered NK cells to potentially supply a life cycle’s worth of commercial off-the-shelf product from a single donor. The methods entail sequential pulses with a proprietary K562 stimulatory cell line in the presence of IL-2 and use of IL-12 and IL-18 to achieve differentiation into memory-like NK cells. When these methods were used to achieve cell expansion greater than even 2 billion-fold, CAR expression was increased on the NK cell surface, engineered cells with CISH gene knockout, CAR and mbIL-15 were preferentially enriched during expansion, and the chromosomal integrity of the cells was well maintained.

Title: KIR Haplotype Can Inform Donor Selection in the Production of Allogeneic Memory-Like CAR NK Cells for Clinical Application
Abstract Number and Type: 128, poster
Poster Presentation Date and Time:November 13, 2021, 7:00 am – 8:30 pm ET
Study findings suggest that the profile of activating and inhibitory KIR genes expressed by healthy donors’ NK cells may serve as a future criterion for selecting donors whose NK cells can be engineered for enhanced cytotoxic activity. The optimal KIR profile may depend on the process used to generate NK cells. Engineered CD19 CAR NK cells whose expansion includes IL-12 and IL-18 added to a proprietary K562 stimulatory cell line containing mbIL-15 and 15-41BBL stimulatory cells showed enhanced potency and upregulation of NK memory associated cell surface markers and natural cytotoxicity markers. Finally, donor KIR haplotype correlated best with CAR NK activity in cells expanded in the presence of IL-12 and IL-18, showing that donor selection and expansion methods must be considered together for development of optimal CAR NK therapies.

* Presented jointly with CRISPR Therapeutics