Th1 vaccination priming for active immunotherapy
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Publication Number
US-11833173-B2
Publication Date
2023-12-05
Expiration Date
Abstract
The present invention includes vaccine compositions and methods for using these vaccine compositions in active immunotherapy. The vaccine compositions include allogeneic activated Th1 memory cells. The compositions can also include one or more disease-related antigens. The methods include administering the vaccine compositions to provide a Th1 footprint in normal individuals or patients susceptible to disease or having minimal residual disease.
Core Innovation
The invention provides an active immunotherapy strategy for treating an individual susceptible to one or more diseases by developing anti-alloantigen immunity. The method administers a priming composition comprising allogeneic activated Th1 memory cells prophylactically, prior to onset of the one or more diseases, and the immune system increases the titer of circulating anti-alloantigen specific Th1 cells, thereby establishing a circulating Th1 “footprint” prior to administration of one or more disease-related antigens.
For disease onset or recurrence, the method administers an activating composition comprising allogeneic activated Th1 memory cells and the one or more disease-related antigens to the primed individual at or after onset. The activating composition and the disease-related antigens are used to suppress the one or more diseases by further increasing the titer of circulating Th1 cells in the individual, and the approach is described in the context of overcoming immune evasion mechanisms and steering subsequent responses toward Th1.
The disclosed priming composition includes that the allogeneic Th1 memory cells are activated by the cross-linking of CD3 and CD28 surface molecules at the time of formulation and administration. The priming composition further includes cross-linking agents for cross-linking the CD3 and CD28 surface moieties on the Th1 memory cells, and the nonclinical discussion includes murine BCL1 tumor data showing Th1 polarization, alloantigen-specific Th1 responses, and improved survival with priming and booster schedules, including enhanced outcomes when combined with cryoimmunotherapy.
Claims Coverage
The independent claim describes a two-stage regimen with three core inventive features: prophylactic priming to establish anti-alloantigen immunity with circulating anti-alloantigen specific Th1 cells, activation by CD3/CD28 cross-linking at formulation and administration, and therapeutic activation with disease-related antigens at or after disease onset or recurrence to suppress disease by increasing circulating Th1 cell titers. Dependent claims further refine booster intervals, booster sourcing, recurrence timing, Th1 balance context, and a post-priming “Th1 footprint” indicator.
Prophylactic priming to develop anti-alloantigen immunity
Administering a priming composition comprising allogeneic activated Th1 memory cells prophylactically, prior to onset of one or more diseases, where the immune system increases the titer of circulating anti-alloantigen specific Th1 cells and the anti-alloantigen immunity is developed prior to administration of one or more disease-related antigens.
CD3/CD28 cross-linking activation at formulation and administration
Activating the allogeneic Th1 memory cells by the cross-linking of CD3 and CD28 surface molecules at the time of formulation and administration, wherein the priming composition comprises allogeneic Th1 memory cells and cross-linking agents for cross-linking the CD3 and CD28 surface moieties on the Th1 memory cells.
Activating composition with disease-related antigens after disease onset
Administering an activating composition comprising allogeneic activated Th1 memory cells and the one or more disease-related antigens to the primed individual at or after the onset of the one or more diseases, wherein the one or more diseases is caused by a pathogen and is suppressed by the increase in the titer of the circulating Th1 cells in the individual.
Overall, the claim coverage focuses on inducing a circulating anti-alloantigen specific Th1 presence via prophylactic priming with CD3/CD28 cross-linking-activated allogeneic Th1 memory cells, then using an activating composition with disease-related antigens administered at or after disease onset or recurrence to suppress pathogen-caused disease through increased circulating Th1 cell titers. Dependent claims further refine booster timing and sourcing, recurrence timing, a Th1 balance context, and the presence of a post-priming “Th1 footprint” indicator.
Stated Advantages
Suppressing one or more diseases caused by a pathogen by increasing the titer of the circulating Th1 cells in the individual.
Developing anti-alloantigen immunity prior to administration of one or more disease-related antigens.
Establishing a circulating Th1 “footprint” prior to disease onset.
Improved survival in a nonclinical murine BCL1 tumor model with priming and booster schedules.
Enhanced outcomes when combined with cryoimmunotherapy and intratumoral/allogeneic Th1 therapy.
Documented Applications
Treating a susceptible individual for one or more diseases caused by a pathogen using an active immunotherapy approach based on prophylactic priming and subsequent activating administration with disease-related antigens.
Cancer therapy, including nonclinical murine BCL1 tumor model evaluation of Th1 polarization, alloantigen-specific Th1 responses, and survival outcomes, including combination with cryoimmunotherapy.
Infectious diseases, including HIV/AIDS, hepatitis C, tuberculosis, and malaria, are described as disease contexts for the method.
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