Placental-derived Natural Killer (PNK) Cells
CYNK-001 is the only cryopreserved, allogeneic, off-the-shelf, natural killer (NK) cell therapy being developed from placental hematopoietic stem cells as a potential treatment option for various hematologic cancers, solid tumors, and infectious disease. NK cells are a unique class of immune cells, innately capable of targeting cancer cells and interacting with adaptive immunity.
CYNK-001 demonstrates a range of biological activities expected of NK cells, including expression of perforin and granzyme B, cytolytic activity against hematological tumors and solid tumor cell lines, and secretion of immunomodulatory cytokines such as IFN-γ in the presence of tumor cells. CYNK-001 cells express NKG2D and CD94, as well as NK activating receptors DNAM1, NKp30, NKp46, and NKp44.
We are investigating CYNK-001 in the clinic as a treatment for multiple cancer indications—multiple myeloma (MM), acute myeloid lymphoma (AML), and glioblastoma multiforme (GBM)—as well as for the emerging infectious disease, COVID-19.
Preclinical studies show that CYNK-001 displays cell killing activity against MM cells, AML cells, GBM cells, and SARS-CoV-2-infected cells in vitro. We are investigating CYNK-001 in vivo and expect it to work by augmenting the body’s natural immune response.
Acute Myeloid Leukemia
Achieve durable response for newly diagnosed AML patients in frontline setting
Newly diagnosed AML patients
Global Incidence in 2019
40,000 new AML cases
Achieve durable response for MM patients eligible for ASCT in frontline setting
Newly diagnosed MM patients following stem cell transplant
Global Incidence in 2019
70,000 new MM patients
Genetically-modified PNK Cells
We are developing CYNK-101 as a combination treatment for multiple cancer indications. CYNK-101 is manufactured from a specific type of immune cell, NK cells, that we extract from postpartum placentas and then genetically engineer to increase cell killing activity when introduced together with an antibody-based anti-cancer treatment.
Preclinical studies show that CYNK-101 plus an antibody therapeutic displays cell killing activity against lymphoma cells in vitro. We expect CYNK-101 to work in vivo by augmenting antibody-dependent cytotoxicity (ADCC), increasing the efficacy of already-approved antibody therapeutics.
We are also engineering PNKs to directly recognize tumor cells even in the absence of the appropriate signals by expressing chimeric antigen receptors (CARs) on their surface. This enhances anti-tumor activity even when tumors express high levels of inhibitory ligands.
CYNK-101 augments ADCC against tumor targets in combination with monoclonal antibodies
Natural Killer (NK) cells are part of the innate immune system and they produce cytotoxic and cytokine effector responses against stressed cells such as virally infected and tumor cells. The hallmark of NK cell function is the natural mechanisms by which they recognize cancerous or virus-infected cells, become activated, and subsequently eradicate those cells. We are developing pipeline programs dedicated to augmenting NK cells’ anti-cancer functions through various genetic modification approaches.
CYNK-101 is an allogeneic, off-the-shelf, NK cell product derived from human placental hematopoietic stem cells and gene-modified to express high-affinity and cleavage-resistant CD16 (FCGRIIIA) variant.
One of the key mechanisms of NK cell effector function is Antibody-Dependent Cellular Cytotoxicity (ADCC), a response driven by CD16 receptors. However, the affinity and durability of the response by native CD16 receptors are regulated by polymorphism and activation-induced receptor shedding. To augment and sustain ADCC responses, we have developed the CYNK-101 product pipeline for combination with tumor-targeting monoclonal antibodies.
In vitro studies have shown higher and sustained ADCC responses by CYNK-101 in combination with monoclonal antibodies against hematological and solid tumors.
Natural Killer Chimeric Antigen Receptor Cells
CYNK-CAR candidates are being developed as allogeneic, off-the-shelf approaches through gene modification of human placental hematopoietic stem cell-derived natural killer (NK) cells. Various CAR constructs against hematological and solid tumor targets are under pre-clinical evaluation.
NK cell activation is governed by the balance of activation and inhibitory signaling. CAR expression on NK cells augments anti-tumor response in one of two ways, by either supplementing tumor recognition in the absence of appropriate activating ligand expression on tumors or tipping the signaling balance in favor of activation when tumor cells express high levels of inhibitory ligands.
Several CAR constructs targeting hematological and solid tumor indications are currently under development.
CAR expression augments tumor recognition and anti-tumor cytotoxicity
The FDA clearance of our IND validates the versatility of our allogeneic, off-the-shelf, placental-derived NK cell therapy platform to generate novel clinical candidates against a broad range of devastating cancers. This IND represents a significant step toward a potential immunotherapy option that is more accessible and tolerable to patients with glioblastoma multiforme.
– Robert J Hariri, MD, PhD