GT Biopharma announced its Tri-Specific Killer Engager can target HIV infected cells in University of Minnesota's preclinical testing.
In preclinical testing led by Drs. Jeffrey Miller, MD, Deputy Director Masonic Cancer Center and Timothy Schacker, MD, Medical School and Director, Program In HIV Medicine, the research team designed a series of Bi- and Tri- Specific killer-engager (BiKE and TriKE) constructs to direct Natural Killer cell antibody dependent cell-mediated cytotoxicity against an HIV infected target.
The data demonstrate that a (BiKE) construct containing the Fab of an HIV bnAb and an anti-CD16 component can eliminate HIV-infected targets that express the HIV envelope on their their surface. Based on the success of the BiKE data, GT Biopharma has now expanded the BiKE's capabilities to be included in the TriKE platform, which the company believes will have further abilities to extend the cytolytic activity currently being demonstrated in its BiKE.
"According to the World Health Organization, there are over 36 million people currently infected with HIV,” CEO, GT Biopharma, Inc., Anthony Cataldo said. “The current drugs available to HIV patients only treat the symptoms of HIV at a massive economic cost. They remain infected for the rest of their lives on theses drugs and at risk for serious infections and certain cancers, while still being infectious to others. The TriKE/BiKE represents the possibility of a cure."
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"Individuals well controlled on anti-retroviral therapy are not cured and dependent on continuous use of their medications. The challenge in the HIV field is to target the reservoir where HIV hides in tissue CD4 T cells and to destroy those sanctuary sites," said Dr. Schacker.
HIV harms the immune system by destroying the white blood cells that fight infection. The virus can be transmitted through contact with infected blood, semen, or vaginal fluids. The disease is usually asymptomatic until it progresses to AIDS (acquired immunodeficiency syndrome). No cure exists for AIDS, but strict adherence to antiretroviral therapy can dramatically slow the disease's progress and prolong life.
GTB-1550 targets cancer cells expressing the CD19 receptor or CD22 receptor or both receptors thereby maximizing cancer cell recognition by binding to CD19+, CD22+ and CD19+/CD22+ cancer cells. When GTB-1550 binds to cancer cells, the cancer cells internalize GTB-1550, and are killed due to the action of drug's cytotoxic diphtheria toxin payload. GTB-1550 has demonstrated success in a Phase 1/2 human clinical trial in patients with relapsed/refractory B-cell lymphoma or leukemia.
At the time of the interim review, 13 patients met the evaluation criteria, including nine NHL and four ALL patients. More than 50% of patients (seven of 13) exhibited a clinical benefit, defined as stable disease, partial remission or complete remission at Day 29. Of the seven patients, one demonstrated a complete remission (CR), one demonstrated a partial remission (PR) and five demonstrated stable disease (SD). The GTB-1550 Phase 1/2 clinical trial is being led by Dr. Veronika Bachanova, Associate Professor of Medicine, Division of Hematology, Oncology and Transplantation at the University of Minnesota.
GTB-3550 (OXS-3550) is the Company's first Tri-specific Killer Engager (TriKE) product candidate being initially developed for the treatment AML. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. When the NK stimulating cytokine human IL-15 is used as a crosslinker between the two scFvs, it provides a self-sustaining signal that activates NK cells and enhances their ability to kill. We intend to study this anti-CD16-IL-15-anti-CD33 tri-specific killer engager, or TriKE, in CD33 positive leukemias, a marker expressed on tumor cells in AML, myelodysplastic syndrome, or MDS, and other hematopoietic malignancies. CD33 is primarily a myeloid differentiation antigen with endocytic properties broadly expressed on AML blasts and, possibly, some leukemic stem cells. CD33 or Siglec-3 (sialic acid binding Ig-like lectin 3, SIGLEC3, SIGLEC3, gp67, p67) is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells. The anti-CD33 antibody fragment that will be used for these studies was derived from the M195 humanized anti-CD33 scFV and has been used in multiple human clinical studies. It has been exploited as target for therapeutic antibodies for many years. Improved survival seen in many patients when the antibody-drug conjugate gemtuzumab was added to conventional chemotherapy validates this approach. GT Biopharma believes that GTB-3550 could serve as a relatively safe, cost-effective, and easy-to-use therapy for resistant/relapsing AML and could also be combined with chemotherapy as frontline therapy thus targeting the larger patient population.