A Simple Approach to Convert IVIG into Neutralizing Anti-Coronavirus Antibodies
Antibodies against the coronavirus that causes COVID-19 have significant therapeutic value, but are limited in supply. The only available source is blood plasma harvested from convalescent patients, whose encounter with the disease has left them (at least temporarily) with COVID-19 immunity. Kleo’s proprietary chemical engineering process takes intravenous immunoglobulin (IVIG)—ordinary human antibodies, which are abundant and available “off-the-shelf”—and converts them into antibodies that target SARS-Co-V2, the virus that causes COVID-19—effectively creating a hyperimmunoglobulin mimic (HGM). Kleo’s technology, called MATE™(Monoclonal Antibody Therapy Enhancement), is a revolutionary approach to the chemical engineering of antibodies for human use. Its application to COVID-19 is in active development and expected to be available for human testing by January 2021. Kleo recently received a grant from The Bill & Melinda Gates Foundation to accelerate the advancement of this technology to the clinic.
ATTACKING THE VIRUS
(1) Blocking the virus. HGM binds the spike protein on the coronavirus surface, preventing the virus from binding the ACE2 receptor on human cells. Kleo has shown that an analogous approach is effective in treating HIV.
(2) Enlisting immune cells. HGM recruits immune cells, such as NK cells and macrophages, to virus particles and virus-infected cells thus leading to the destruction of these disease-causing and diseased entities.
(3) Activating long-term immunity. By delivering viral proteins to antigen presenting cells, HGM facilitates the priming and activation of immune memory cells (e.g. T-cells) to instill long-term immunity like a conventional vaccine.
COVID-19 Antibody Recruiting Molecule (ARM)
No human population has natural immunity to SARS-CoV-2, the virus that causes COVID-19. Kleo has developed a technology that can be adapted to fight the virus and create immunity where none previously existed.. Kleo’s antibody recruiting molecule (ARM™) is a synthetic molecule—not biological in origin—that can be modified to recruit a patient’s immune system to attack a target of choice. ARMs have been developed to successfully target specific cancer cells, fungal cells, and viruses. ARM is a “plug-and-play” platform. We choose the target and adapt the molecule to attack it directly, or recruit the immune system to fight it.
COVID-19 Antibody Recruiting Molecule (ARM)+Allogeneic NK Cell Combination Therapy
Kleo has initiated two research collaborations, with South Korea-based GC LabCell and US-based Celularity Inc. to investigate using our ARM+NK cell combination therapy approach to combat COVID-19. We previously demonstrated a synergistic effect of using our ARM to enhance the anti-tumor efficacy of autologous NK cells. Now we are using the same approach in COVID-19 with allogeneic, or “off-the-shelf”, NK cell therapies. The innate immune cells have been shown to aid in viral clearance both directly and indirectly (cytokine secretion) but are not targeted to specific protein targets like the T cells of the adaptive immune response. Kleo’s ARM, in combination with NK cell therapies, are expected to target the therapies to the site of infection and to synergistically improve viral clearance and improve efficacy.