So smart to put this up on their homepage. Nothing like it from LP but she’s a lawyer, of course. Anything like it from Liau?
>>Founder’s Hypothesis
For the past 35 years, through my experience at UCLA treating both diabetic patients with pancreas transplants, and pancreatic cancer patients with pancreatic surgery (Whipple’s), I realized that the body had opposing immune systems: on the one hand, cytotoxic systems to reject the transplanted pancreas and on the other hand immuno-evasion systems to allow pancreatic cancer to grow. By 1990, I came to realize that the common denominator was the NK cell which on the one hand interacted with killer T cells to reject a transplanted organ and on the other hand, the killer NK and T cells were blocked by the tumor, allowing the tumor cells to grow.
At that time, I realized that the very therapy patients were receiving (high-dose chemotherapy and radiation) aided in the destruction of the very cells patients needed to cure cancer. Of concern was the realization that the standards-of-care physicians were pursuing were based on the assumption that killing the tumor and achieving a short-term response would win the war against cancer.
In fact, a short-term battle would be won by observing a response rate, but the war lost because of the destruction of important cells called lymphocytes by our chemotherapy and radiation treatment, preventing the formation of memory T cells and long-term duration of response – duration matters, T cell memory matters. Thus began the hypothesis that if we could harness the activity of lymphocytes – specifically NK and killer T cells, the potential existed to outsmart the immuno-evasion of cancer and unleash the body’s immune system to treat cancer with immunotherapy for long-term overall survival and indeed even prevent cancer in patients with high risk.
However, I faced the challenge of overcoming 50 years of standards of care which relied on high-dose chemotherapy and radiotherapy. The notion that the standard-of-care would rapidly destroy these lymphocytes, the very cells needed to kill the tumor and establish T and NK cell memory, was difficult to convince the medical establishment and regulatory authorities. The possibility that our standard-of-care was indeed responsible for preventing long-term complete remissions by the inadvertent process of destroying the very system engineered in our bodies to protect against cancer and infectious disease, was the quest that required challenging. That is the mission of ImmunityBio and the recent recognition in 2025 by the FDA that ANKTIVA and PD-L1 t-haNK was granted a Regenerative Medicine Advanced Therapy (RMAT) designation for the reversal of lymphopenia in patients receiving chemotherapy and radiation therapy is a turning point for this paradigm change in cancer care.
The destruction of the NK and T cells resulting in lymphopenia (low levels of lymphocytes) correlated with poor prognosis of overall survival across multiple tumor types. With our increasing knowledge of the immune system, including the discovery of T cells, NK cells and dendritic cells, and their role in cancer suppression (immuno-surveillance) and cancer growth when the tumor develops mechanisms to hide from the cytotoxic effects of NK and T cells (immune evasion), it became time to re-visit immunotherapy. Most are familiar with the breakthrough of CPI therapy, represented by antibodies that target either PD-1, PD-L1, or other molecules that act to inhibit immune cell (specifically T cell) responses to cancer. But even the efficacy of CPI therapies can be undermined by lymphopenia (lack of T cells), making the rescue of lymphopenia an overarching goal of my approach to cancer therapy.
This vision, which I have pursued for decades, is the transformation in the paradigm for cancer care by treating the host and activating the immune system (NK cell and killer T cell) resulting in immunogenic cell death and inducing long-term duration of response with the generation of memory T cells and memory NK cells. On the other hand, standards of care have been addressing the tumor itself (rather than the host immune system) with high-dose chemotherapy for short-term response gains.
A paradigm change would be to utilize the tumor itself in the body as an antigenic, vaccine source to generate long-term memory resulting in a durable response to the activated NK cell, T cell and memory T cell. In this way, a therapeutic cancer vaccine could be developed. Along this journey, it has been difficult to convince academia, medical cancer centers, the FDA and even the pharmaceutical industry that existing treatment paradigms for cancer are based on misplaced assumptions of administering high-dose chemotherapy and radiotherapy by “winning the battle but losing the war.” Duration of response matters and NK cells, T cells, and memory T cells are key to prolonging overall survival.
In 2017, I proposed a General Investigational Plan to study a potential therapeutic cancer vaccine applicable to all tumor types to the FDA and was given an audience with the Oncology Centers of Excellence by the FDA leadership. The hypothesis, including the request for RMAT designation presented in the plan was as follows:
A paradigm change in cancer care is required in which a modernized treatment is based on the biology of the tumor independent of anatomy, utilizing molecular and immunological insights as to the dynamic state of the cancer in its evolution (elimination, equilibrium, and escape) and specifically tailored to the patient’s cancer altered genome, to reinstate the patient into equilibrium.
The notion that the tumor tissue itself could act as a source of both antigenicity and adjuvanticity is exploited by the NANT Cancer Vaccine – a universal therapeutic cancer vaccine that acts through the orchestration of the innate and adaptive immune system across all tumor types.
We hypothesize that the normal physiological protective immune system of Elimination can be reinstated by the NANT Cancer Vaccine, first by overcoming the immunosuppressed Escape state, followed by induction of immunogenic cell death and activation of effector immune cells, with restoration of the patient to a state of Equilibrium, a paradigm change in cancer care.
The leadership at the FDA listened to this presentation and subsequently while denying RMAT designation, authorized my request to pursue this hypothesis by performing Phase 1 and Phase 2 clinical trials I termed “QUILT” QUantum Integrative Lifelong Trial across certain indications including first-line and second-line NMIBC, second-line and third-line MCC, second-line and third-line metastatic pancreatic cancer, second-line or greater GBM, third-line metastatic TNBC and third-line metastatic head & neck cancer. I also coined the term “Quantum Oncotherapeutics” to highlight the concept that the TME is dynamic and very rapid changes occur based on the therapy we administer.
For the first time in 50 years, oncologists may now have a reason to pay more attention to a complete blood count analysis of lymphocytes (NK & T cells) as the RMAT designation – granted on February 27, 2025 for ANKTIVA and PD-L1 t-haNK in combination with standard-of-care chemotherapy/radiotherapy indicated for the reversal of lymphopenia and treatment of multiply relapsed locally advanced or metastatic pancreatic cancer – is developed. Below is a summary of this journey. It is my hope that the concept of ALC will begin to be recognized by oncologists and the ratio of ANC to ALC will become a key biomarker of the current status of a patient with cancer and a predictor of outcome.
AI
