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Publication Number
US-11213576-B2
Publication Date
2022-01-04
Expiration Date
Abstract
The invention disclosed herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues by first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing necrosis or apoptosis in a tumor or pathogen infected lesion by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue, and then delivering one or more doses of allogeneic cells (e.g., Th1 cells) within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.
Core Innovation
The invention provides a therapeutic composition and a vaccine that combine pathogen antigens derived from pathogen-infected tissue subjected to necrosis with allogeneic activated T-cells associated with nanobeads. The pathogen antigens comprise chaperone proteins, and antigen-presenting cells in the patient uptake the antigens and subsequently mature in the patient to systemically stimulate anti-pathogen immunity.
The allogeneic cells are CD4+Th1 cells producing in excess of 2000 ng/ml/10^6 cells/6 hours of IFN-b3. The CD4+Th1 cells are produced by normal donor T-cells expanded by CD3/CD28 T-cell expander beads, harvested after expansion, debeaded, and then incubated with nanobeads conjugated to antibodies that bind to CD3 and CD28 cell surface moieties to cross-link CD3/CD28 on the T-cells prior to infusion.
For the vaccine embodiment, the allogeneic cells create a rejection response and stimulate a delayed-type hypersensitivity response in the patient to the allogeneic cells. This rejection response and delayed-type hypersensitivity response act as an adjuvant to the stimulation of systemic anti-pathogen immunity, and the antigenic material is generated by necrosis of a lesion.
Claims Coverage
Two independent claims are present. Both independent claims focus on a combination of pathogen antigenic material containing chaperone proteins from necrosis of pathogen-infected tissue with nanobead-associated allogeneic activated CD4+Th1 cells.
Therapeutic composition with necrosis-derived pathogen antigens and nanobead-associated allogeneic CD4+Th1 cells
A therapeutic composition for treating a pathogen comprising pathogen antigens from pathogen infected tissue subjected to necrosis, where the pathogen antigens comprise chaperone proteins, and allogeneic activated T-cells associated with nanobeads suspended in media suitable for injection, wherein the allogeneic T-cells serve as an adjuvant to create an immune response and antigen-presenting cells in the patient uptake the antigens and subsequently mature to systemically stimulate anti-pathogen immunity.
IFN-gamma-producing CD4+Th1 cells cross-linked via CD3/CD28 prior to infusion
The therapeutic composition wherein the allogeneic cells are CD4+Th1 cells producing in excess of 2000 ng/ml/10^6 cells/6 hours of IFN-gamma, and the CD4+Th1 cells were produced by normal donor T-cells expanded by CD3/CD28 T-cell expander beads, harvested after expansion, debeaded, and incubated with nanobeads conjugated to antibodies that bind to CD3 and CD28 cell surface moieties for cross-linking of CD3/CD28 on the T-cells prior to infusion.
Vaccine with necrosis-generated antigenic material containing chaperone proteins and nanobead-associated allogeneic CD4+Th1 cells
A vaccine for a patient against a pathogen comprising antigenic material from tissue infected by the pathogen, where the antigenic material comprises chaperone proteins, and allogeneic activated T-cells associated with nanobeads suspended in media suitable for injection, wherein the allogeneic cells create a rejection response and stimulate a delayed-type hypersensitivity response in the patient to the allogeneic cells thereby acting as an adjuvant to the stimulation of systemic anti-pathogen immunity.
Necrosis lesion-derived antigenic material and Th1 IFN-gamma threshold with CD3/CD28 cross-linking prior to infusion
The vaccine wherein the antigenic material is generated by necrosis of a lesion, and wherein the allogeneic cells are CD4+Th1 cells producing in excess of 2000 ng/ml/10^6 cells/6 hours of IFN-gamma, produced by normal donor T-cells expanded by CD3/CD28 T-cell expander beads, harvested after expansion, debeaded, and incubated with nanobeads conjugated to antibodies that bind to CD3 and CD28 cell surface moieties for cross-linking of CD3/CD28 on the T-cells prior to infusion.
Across both independent claims, the coverage centers on necrosis-associated pathogen antigenic material comprising chaperone proteins combined with nanobead-associated allogeneic activated CD4+Th1 cells that produce high levels of IFN-gamma. The claims further emphasize that antigen uptake and maturation by antigen-presenting cells and systemic anti-pathogen immunity are stimulated, with the vaccine embodiment explicitly requiring a rejection response and delayed-type hypersensitivity response acting as an adjuvant.
Stated Advantages
Systemically stimulates anti-pathogen immunity in the patient via uptake and maturation of the antigens by antigen-presenting cells.
Acts as an adjuvant through creation of a rejection response and stimulation of a delayed-type hypersensitivity response to enhance systemic anti-pathogen immunity.
Uses CD4+Th1 cells producing in excess of 2000 ng/ml/10^6 cells/6 hours of IFN-gamma as the adjuvant immune cells.
Documented Applications
Treating a patient for a pathogen using a therapeutic composition comprising pathogen antigens from pathogen-infected tissue subjected to necrosis together with allogeneic activated CD4+Th1 cells associated with nanobeads.
Vaccinating a patient against a pathogen using a vaccine comprising antigenic material from pathogen-infected tissue necrosis together with allogeneic activated CD4+Th1 cells associated with nanobeads.
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