Immunofusion is a biotechnology company, founded in 2020. The company focused on the discovery, development, and commercialization of synthetic DNA products for cancer and infectious diseases immunotherapy. Our company develops a number of innovative drug designs including DNA vaccines, immunocytokines, genetic modifications and CAR-T cell therapy.
A novel tandem CAR-T for MCL and CLL
The 4th generation tandem chimeric antigen receptor (TanCAR) for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).
TanCAR recognizes two functionally cross-talking targets on CLL or MCL cells — patient-specific BCR that could be matched in up to 70% of MCL and 50% of CLL, and ROR1. A proprietary synthetic nanobody library was used for ROR1-specific nanobodies generation.
The signaling domain of TanCAR includes a novel cytokine domain that ensures the resistance of СAR-modified T-cells to functional exhaustion and maintains their persistence.
Currently, FDA approved CAR T-therapies for B-cell lymphomas have a number of limitations resulting in a poor response for CLL and MCL: on-target off-tumor toxicity, antigen escape, CAR T-cell dysfunction due to exhaustion, and senescence. Dual targeting of patient-group-specific BCRs and ROR1 prevents B-cell aplasia and antigen loss. The inclusion of a cytokine domain in CAR T gives a signal 3 for T-cell upon antigen stimulation and thus provides resistance to exhaustion and improves persistence.
The new treatment platform is comprised of 4 different immunocytokines, which are delivered by the means of nucleic acids (RNA or DNA) for the in vivo expression.
Every immunocytokine biomolecule consists of a targeting unit (scFv or VHH) specific to a tumor associated antigen, interleukin and a costimulatory molecule. The treatment modality assumes an exposure to 4 different immunocytokines simultaneously, each fulfiIling its own but complementary function for efficient anti-tumor immune-response engagement delivering signal 2 and signal 3 in TME.
The main function is to accomplish DC homing and maturation in the tumor microenvironment (TME), homing of T-cell and NK-cells to TME, and activating different chains of the immune system directly in the immunosuppressive TME.
Such a therapeutic approach could be an independent treatment modality to release all pathways of endogenous anticancer immunity as well as an additive therapy to any cellular therapy (CAR-T cells, NK cells) or cancer vaccine to enhance anticancer efficacy.
Immunofusion is attending #BIOEuropeSpring! Join us in Basel March 20-22, 2023 and let’s meet!
Thanks to Simone Haubner and Robert Möbius for sightseeing tour in Leipzig Biopark. Great place with lots of opportunities.
Great week on Bio 2022.BIO-Europe is the place to meet the world under one roof and discover the latest innovations which will advance the medicines of tomorrow. Thanks to all the participants for opportunities and new friends.
TransCure bioServices starting a new one pilot study in CD34+ humanized mice engrafted with tumor cells in our Immunocytokine compositions project.
An emerging COVID‑19 pandemic resulted in a global crisis, but also accelerated vaccines development and antibodies discovery. By screening of the more than 1011 diversity synthetic humanized VHH antibody library against different SARS-CoV-2 variants of concern (VoC) receptor binding domain (RBD) we have identified a number of nanomolar-range affinity binders. In order to explore the most robust and fast method for affinity improvement we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, their affinities are weakly influenced by SARS-CoV2 VoC mutations. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies respectively for emerging Omicron variant. Therefore, these VHH could be expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.
1. Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Front Immunol. 2022 Sep 16;13:965446. doi: 10.3389/fimmu.2022.965446. PMID: 36189235; PMCID: PMC9524272.
2. Meleshko A, Piatrouskaya N, Vashkevich K, Lutskovich D, Wang C, Dormeshkin D, Savelyeva N, Katsin M. Safety and Immunogenicity of Combined DNA-Polyethylenimine and Oral Bacterial Idiotypic Vaccine for Patients with B-Cell Non-Hodgkin Lymphoma: A Pilot Study. Cancers (Basel). 2022 Jul 6;14(14):3298. doi: 10.3390/cancers14143298. PMID: 35884359; PMCID: PMC9320637.
3. Dormeshkin D, Shapira M, Karputs A, Kavaleuski A, Kuzminski I, Stepanova E, Gilep A. Combining of synthetic VHH and immune scFv libraries for pregnancy-associated glycoproteins ELISA development. Appl Microbiol Biotechnol. 2022 Aug;106(13-16):5093-5103. doi: 10.1007/s00253-022-12022-w. Epub 2022 Jun 20. PMID: 35723693.
4. Meleshko AN, Petrovskaya NA, Savelyeva N, Vashkevich KP, Doronina SN, Sachivko NV. Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma. Hum Vaccin Immunother. 2017 Jun 3;13(6):1-6. doi: 10.1080/21645515.2017.1285477. Epub 2017 Mar 8. PMID: 28272989; PMCID: PMC5489279.
5. Stepanov AV, Markov OV, Chernikov IV, Gladkikh DV, Zhang H, Jones T, Sen’kova AV, Chernolovskaya EL, Zenkova MA, Kalinin RS, Rubtsova MP, Meleshko AN, Genkin DD, Belogurov AA Jr, Xie J, Gabibov AG, Lerner RA. Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma. Sci Adv. 2018 Nov 14;4(11):eaau4580. doi: 10.1126/sciadv.aau4580. PMID: 30443597; PMCID: PMC6235538.
6. Shman TV, Vashkevich KP, Migas AA, Matveyenka MA, Lasiukov YA, Mukhametshyna NS, Horbach KI, Aleinikova OV. Phenotypic and functional characterisation of locally produced natural killer cells ex vivo expanded with the K562-41BBL-mbIL21 cell line. Clin Exp Med. 2022 Dec 17. doi: 10.1007/s10238-022-00974-2. Epub ahead of print. PMID: 36527513.
7. Aleinikova O.V., Migas A.A., Stolyarova E.A., Punko A.V., Movchan L.V., Klych A.V., Mishkova O.A., Hill A.V., Meleshko A.N., Konoplya N.E. The fist experience of using locally manufactured CAR-T cells in patients with relapsed/refractory acute lymphoblastic leukemia in Belarus. Pediatric Hematology/Oncology and Immunopathology. 2021;20(2):30-38. (In Russ.) doi: 10.24287/1726-1708-2021-20-2-30-38
Volkov Oleg, MD
Chief Executive Officer
Dormeshkin Dmitri, PhD
Chief Technology Officer
Katsin Mikalai, MD
Chief Scientific Officer
Meleshko Alexander, PhD
Head of Preclinical Models and Cancer Vaccines Unit
Head of Cellular Engineering Department