Methods of preparing anti-human papillomavirus antigen T cells
Inventors
Hinrichs, Christian S. • Rosenberg, Steven A.
Assignees
US Department of Health and Human Services
Publication Number
US-11331385-B2
Publication Date
2022-05-17
Expiration Date
2034-07-14
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed are methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells comprise dividing an HPV-positive tumor sample into multiple fragments; separately culturing the multiple fragments; obtaining T cells from the cultured multiple fragments; testing the T cells for specific autologous HPV-positive tumor recognition; selecting the T cells that exhibit specific autologous HPV-positive tumor recognition; and expanding the number of selected T cells to produce a population of HPV-specific T cells for adoptive cell therapy. Related methods of treating or preventing cancer using the T cells are also disclosed.
Core Innovation
The invention provides methods of preparing an isolated population of human papillomavirus (HPV)-specific T cells by dividing an HPV-positive tumor sample into multiple fragments, separately culturing these fragments, obtaining T cells from the cultured fragments, testing the T cells for specific autologous HPV-positive tumor recognition or HPV antigen recognition, selecting the T cells exhibiting such recognition, and expanding the selected T cells to produce a population of HPV-specific T cells intended for adoptive cell therapy.
The methods described include culturing tumor fragments in the presence of only one cytokine, preferably interleukin-2 (IL-2), and expanding T cells using one or both of OKT3 antibody and IL-2, optionally combined with irradiated allogeneic or autologous feeder cells. The invention also provides methods of treating or preventing cancer by administering these expanded HPV-specific T cells to a mammal, in an amount effective to treat or prevent HPV-associated cancer.
The problem being addressed is the poor prognosis for many cancers caused by HPV infection, such as uterine cervical cancer, despite advances in chemotherapy and other treatments. There exists an unmet need for additional treatments for HPV-associated cancers, as standard therapies may not adequately address these cancers or may cause significant toxicity.
Claims Coverage
The patent contains one independent claim comprising multiple inventive features related to culturing and expanding HPV-specific T cells for treatment of cervical cancer.
Culturing HPV-positive tumor fragments in presence of IL-2
Multiple fragments of an HPV-positive tumor sample from a patient are cultured in the presence of interleukin-2 (IL-2).
Obtaining and expanding T cells using feeder cells and stimulatory agents
T cells are obtained from the cultured fragments and expanded using one or both of irradiated allogenic and autologous feeder cells, and one or both of OKT3 antibody and IL-2 without depletion of CD4+ cells.
Administration of expanded HPV-specific T cells to patient
The expanded population of HPV-specific T cells is administered to the patient in an effective amount to treat or prevent cervical cancer.
These inventive features collectively define a method of preparing and administering HPV-specific T cells by culturing tumor fragments with IL-2, expanding T cells via feeder cells and stimulatory agents, and using said expanded T cells for therapeutic treatment, without depleting CD4+ cells.
Stated Advantages
Generates T cells from HPV-positive cancers at a clinical scale.
Produces T cells that specifically recognize HPV antigens E6 and E7, which are constitutively and specifically expressed by cancer cells, minimizing destruction of normal cells and reducing toxicity.
The method uses nonmyeloablative chemotherapy allowing treatment of patients ineligible for total body irradiation.
Provides successful treatment or prevention of HPV-positive cancers that are unresponsive to other treatments such as chemotherapy, surgery, or radiation.
Documented Applications
Treating or preventing HPV-associated cancers, including cervical cancer, oropharynx, anus, anal canal, anorectum, vagina, vulva, penis, and other HPV-positive cancers.
Preparing HPV-specific T cells for adoptive cell therapy in mammals, particularly humans.
Interested in licensing this patent?