TILT Biotherapeutics Ltd is a preclinical stage company working in the field of cancer immunotherapy.
TILT Biotherapeutics Ltd is a preclinical stage company working in the field of cancer immunotherapy. TILT aims to translate its unique approach into clinical trials. The company’s patented technology involves utilization of oncolytic viruses for enhancement of tumor T-cell therapy. Initial embodiments of the technology will be used to enhance tumor infiltrating lymphocyte (TIL), chimeric antigen receptor (CAR) and checkpoint inhibiting antibody therapy. The TILT approach has the potential to achieve similar results in CAR therapy of solid tumors as currently achieved for CD19+ hematological tumors.
The best results in T-cell therapy trials, especially with tumor-infiltrating lymphocytes (TIL), have been obtained when high dose chemotherapy, with or without whole body irradiation were used as pre-conditioning regimens to enhance the effect of the T-cell graft. In fact, many experts in the field feel that with conventional TIL technology, these highly toxic conditioning regimens are required for efficacy. Moreover, most TIL trials utilize high dose IL-2 (previously known as T-cell growth factor) as a post-conditioning regimen to prolong the activity and viability of the graft. However, both pre- and post-conditioning are toxic regimens causing adverse events including deaths. The patented TILT technology is based on novel oncolytic viruses coding for cytokines. The constructs are unique in structure, sequence and function. Formal patentability and freedom to operate searches have underlined the uniqueness of the TILT approach. While laboratory work has already indicated that TILT technology results in dramatic increases in efficacy in murine models of T-cell therapy, mechanism of action studies are still under way. However, emerging data suggests enhancement of both the recruitment and the anti-tumor activity of the T-cell graft. Importantly, ongoing studies will determine if TILT technology will allow retained or increased efficacy in the absence of pre- and post-conditioning chemotherapy and IL-2, respectively (Figure 1 below). While chimeric antigen receptor (CAR) modified T-cell have already worked well in trials with hematological cancer patients with CD19+ tumors, in solid tumors the results have been disappointing. Our technology has the potential to overcome the identified obstacles for realizing the potential of CAR technology in solid tumors. Thus, with the TILT approach, it may be possible to obtain similar results in solid tumors as currently seen in CD19+ leukemias.
T-cells are collected from tumors (1a) or blood (1b). In the case of 1b, cells are transduced with lentivirus coding for a selected T-cell receptor or chimeric antigen receptor.
T-cells are grown in the laboratory in the presence of IL2, also known as T-cell growth factor. Afterwards the process of returning the T-cells into the patient (intravenously) begins.
Many T-cells stay in the circulation or go to non-target organs insted of tumor. The few cells that make it to the tumor may rapidly become inactivated because of the immune suppressive tumor microenvironment.
TILT virus is injected intratumorally (a) or intravenously (b) and finds its way to the tumor. TILT has patented technology for both intratumoral and intravenous delivery of its oncolytic viruses to tumors.
TILT virus replicates and produces cytokines, resulting in recruitment of T-cells from the circulation. Also, as shown in the blow-up the T-cells at the tumor are activated by the cytokine coding oncolytic virus.
Four posters featuring TILT technology were presented at the 13th Cancer Immunotherapy Annual Meeting in Mainz, Germany in May 2015. With most browsers, you can zoom in on the poster and the resolution will improve. Links to posters can also be found on the News page.
Posters featuring TILT technology were presented at the American Society of Gene & Cell Therapy 19th Annual Meeting in Washington DC, USA in May 2016. Posters can also be found on the News page.
Poster featuring TILT technology will be presented at the European Society of Cell and Gene Therapy Annual Congress in Florence, Italy in October 2016. Poster can also be found on the News page.
Poster featuring TILT technology will be presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington DC, USA in November. Poster can be found also from the News page.
Leukemia patients cured with CAR technology
TILT Biotherapeutics is founded
First randomized phase 3 trial with TIL + low dose IL2 completed
Low-dose IL2 proposed as better tolerated alternative for TIL post-conditioning
“Young TILs” simplify TIL procedure
Response rates near 50% and many melanoma patients seem cured with TIL but with significant toxicity
Engineering of peripheral blood lymphocytes with tumor specific T-cell receptors
High dose chemotherapy proposed as lymphodepleting preconditioning
Preconditioning regimens are compared: high dose chemo +/- full body radiation.
Interleukin 2 is added to the treatment protocol
Chimeric antigen receptor (CAR) technology for targeting peripheral blood lymphocytes
Discovery of the T cell antigen receptor
Adoptive T-cell therapies first tested using tumor infiltrating lymphocytes (TIL)
Generation of the first monoclonal T cells (Kendall A. Smith)
T-cell restriction to MHC (Rolf Zinkernagel and (Peter C. Doherty)
Passenger leukocytes identified as significant immunogens in allograft rejection (William L. Elkins and Ronald D. Guttmann)
Discovery of involvement of the thymus in cellular immunity (Jacques Miller)
Discovery of human leukocyte antigens (Jean Dausset and others)
Discovery of lymphocyte circulation (James Gowans)
Graft-versus-host disease (mediated by T-cells)
Demonstration of organ rejection (mediated by T-cells)
Cutaneous allergic reactions (Otto Prausnitz and Heinz Küstner)
Paul Ehrlich proposes the immune surveillance hypothesis of tumor recognition and eradication
Use of live bacteria and lysates to treat tumors (William B. Coley)
Demonstration of cutaneous delayed type hypersensitivity (Robert Koch)
Edward Jenner discovers the benefits of vaccination
Founder & CEO
Haartmaninkatu 3, 4th floor, C-wing
00290 Helsinki, Finland
akseli at tiltbio dot com
For more information about clinical trials, please see http://en.wikipedia.org/wiki/Clinical_trials For more information about phase 1 trials, please see http://www.cancer.net/all-about-cancer/clinical-trials/phases-clinical-trials To search for clinical trials, please see eg. http://clinicaltrials.gov/ For more information about melanoma, please see http://en.wikipedia.org/wiki/Melanoma For information on T-cell therapy, please see http://en.wikipedia.org/wiki/Immunotherapy#T-cell_adoptive_transfer
Advanced-therapy medicinal product (ATMP) classification was confirmed for TILT-123 by the Committee for Advanced Therapies (CAT) of European Medicines Agency. The report summary can be found here
TILT Biotherapeutics featured in European Biotechnology Vol.15 2016.
Posters featuring TILT technology were presented at the American Society of Gene & Cell Therapy 19th Annual Meeting in Washington DC, USA in May 2016
Culture and Characterization of Tumor-Infiltrating Lymphocytes of the Syrian Hamster
Oncolytic Adenoviruses Armed with TNFa and IL-2 Induce Antitumor Immune Responses and Protection from Tumor Rechallenge
6.5.2016 TILT / University of Pennsylvania (Carl June group) collaboration featured in an oral presentation at the American Society of Cell and Gene Therapy meeting in Washington, DC
March 2016. Aino Kalervo starts as Head of Business Management at TILT
Feb 2016. Víctor Cervera Carrascón starts as a Marie Skłodowska-Curie PhD Student at TILT Biotherapeutics Ltd
Feb 2016. Mona Österlund starts as Head of Clinical Operations at TILT
Jan 2016. João Manuel Santos started as a Marie Skłodowska-Curie PhD Student at TILT Biotherapeutics Ltd
Jan 2016. Elina Koli starts as Head of Quality at TILT
19.9.2015 TILT technology presented in an invited talk at the European
Society of Gene and Cell Therapy meeting http://www.esgct.eu/congress.aspx
TILT Biotherapeutics Ltd, VU University medical center (VUmc) and ORCA Therapeutics announce EU funded Marie Curie Early Stage Researcher positions starting in early 2016.
Application deadline 20.09.2015.
TILT Biotherapeutics featured in Nature Reviews Drug Discovery
Four posters featuring TILT technology were presented at the 13th Cancer Immunotherapy Annual Meeting in Mainz, Germany in May 2015
Suvi Parviainen joins TILT as Head of R&D
First Scientific Advisory Board meeting held
TILT receives 2 year government loan from TEKES
TILT science presented in an invited talk at the European Society of Cell and Gene Therapy
TILT technology featured in an invited presentation at the Oncolytic Viruses Meeting in Oxford, UK
TILT featured in Talouselämä
Akseli Hemminki presents on Oncolytic vaccines for treatment of cancer at the Progress in Vaccination against Cancer meeting in Amsterdam, the Netherlands.
Seed funding round closed following investments by angels, Lifeline Ventures Fund, Finnish government (TEKES) and Finnish Invention Fund (Keksintösäätiö).
TILT Biotherapeutics Ltd is founded