San Diego, CA, United States
San Diego, CA, United States

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Patent
Batu Biologics | Date: 2016-08-03

Disclosed are cells, compositions of matter, and protocols, useful for stimulation of antigen-specific immunity or tolerogenesis by gene editing of immune suppressive costimulatory molecules for induction of immune stimulation, and gene editing of immune stimulatory molecules for immune suppression. Provided are means of stimulating immunity to cancer, viral antigens, or bacterial antigens through pulsing, fusing, or administering antigenic compositions to antigen presenting cells that are gene silenced for immune suppressive genes. Provided are means of treating transplant rejection or autoimmunity by gene silencing immune stimulatory genes.


Patent
Batu Biologics | Date: 2016-01-22

Disclosed are composite cancer vaccines, in one embodiment generated through 3-dimensional bioprinting or through inoculation of roller cultures. The utilization of decellularized biological matrices such as placental tissue or subintestinal submucosal tissue is disclosed as a substrate for 3-dimensional tissue culture. In one embodiment tumor cells are assembled with monocytes and/or mesenchymal stem cells to represent in vivo existing tumors. The invention teaches means of generating off-the-shelf tumor vaccines containing antigenic properties similar to in vivo growing tumors, which cannot be currently replicated under existing 2-dimensional tumor culture means of generating cell lines


Patent
Batu Biologics | Date: 2016-02-08

Disclosed are methods, protocols, and compositions of matter related to utilization of chimeric antigen receptor (CAR) expressing cells for the targeting of tumor endothelium utilizing chimeric antigen receptor expressing stem cells. In one embodiment tumor endothelium specific antigens are utilized as targets of the antigen binding domain of a CAR, which is attached to an extracellular hinge domain, a domain that transverses the T cell membrane and an intracellular domain associated with T cell signaling. Suitable antigens for the practice of the invention include TEM-1, ROBO-4, surviving, and FasL. In other aspects of the invention antigens are identified through serological analysis of recombinant cDNA expression libraries (SEREX) using plasma from a patient immunized with placental endothelial cells.


Disclosed are means of protecting signaling integrity of T cells in cancer patients through reduction of neutrophil and other cellular induced oxidative stress. In one embodiment the FDA approved drug Mucomyst is administered at a concentration of 50-150 mg/kg to increase expression of T cell receptor (TCR)-zeta chain in patients with cancer. In other embodiments enhancement of CAR-T cell therapy is performed through modulation of inflammatory and oxidative stress in a tumor bearing patient.


Patent
Batu Biologics | Date: 2016-02-17

Disclosed are allogeneic cells useful for the treatment of cancer in a universal donor, off the shelf, manner. In one embodiment of the invention cord blood derived T cell progenitors are matured with anti-CD3 and anti-CD28, interleukin-7 and transfected with a construct encoding a chimeric antigen receptor (CAR) targeting a tumor antigen or a tumor endothelial associated antigen on the antigen binding domain. The intracellular domain containing CD3 zeta chain and at least one shRNA domain encoding a transcript which generates at least one siRNA capable of inhibiting expression of HLA I and/or HLA II. In another embodiment mesenchymal stem cells are transfected with CAR to enhance migration into tumors and induce tumor death, reduction of inflammation, or immune sensitization. In another embodiment universal donor CAR-MSC are disclosed.


Patent
Batu Biologics | Date: 2016-05-02

Disclosed is the new, useful, and unexpected finding that immunization to placental endothelial cells stimulated with interferon gamma result in antibodies to the checkpoint inhibitor PD-L1. In one embodiment, the invention teaches the use of ValloVax to induce immunological hyperresponsiveness and reduction of costimulatory need for T cell activation. In another embodiment the invention teaches means of selecting placental populations for enhanced expression of PD-L1 in order to augment immunity towards checkpoint inhibitors.


Disclosed are compositions of matter, methods, and protocols useful for treatment of cancer through induction of anti-angiogenic immune responses. The invention provides means of differentiating tumor cells directly into endothelial or endothelial-like cells and utilizing said cells as immunogens for the purpose of inducing immunity against blood vessels feeding tumors. In one embodiment glioma cells are cultured under hypoxic conditions in the presence of endothelial-differentiating factors. In another embodiment, PECAM-1 positive cells are derived from a tumor mass or cell line and utilized as an antigenic source to induce immunity towards tumor derived endothelial cells, endothelial-like cells, and tumor vascular channels.


Disclosed are protocols, procedures and therapeutic compositions useful for augmentation of immunity to cancer and cancer associated endothelial cells by treatment with histone deacetylase (HDAC) inhibitors capable of augmenting stimulatory and costimulatory molecules on said cancer vaccines. Additionally, the invention teaches specific concentrations of HDAC inhibitors useful for stimulation of in vivo immunity to tumor and tumor endothelial cell targeting vaccines.


Patent
Batu Biologics | Date: 2016-07-06

Disclosed are methods, protocols, and compositions of matter useful for induction and/or propagation of antitumor immune responses through gene editing of immunocytes. Stimulation of antitumor adaptive immunity is achieved through gene editing of autologous or allogeneic lymphocytes in a manner to derepress neoplasia induced suppression. The method can include targets of gene editing disclosed in the current invention include the E3 ubiquitin ligase Cbl-b, CTLA-4, PD-1, TIM-3, killer inhibitory receptor (KIR) and LAG-3.


Patent
Batu Biologics | Date: 2016-05-23

Neutrophil extracellular traps (NETS) are webs of DNA held together with immunogenic peptides, released by neutrophils subsequent to activation. NETS are the most potent stimulator of dendritic cells, monocytes and T cells given their ability to activate TLR3, TLR4, TLR7 and TLR9. The use of NETS for in vivo stimulation of immunity in a therapeutic sense has not been utilized due to fear of anti-DNA antibody formation and subsequent development of systemic lupus erythromatosis. The current invention provides means of safely generating NETS in vitro through peripheral blood utilizing clinically safe means such as yeast-derived component zymosan, isolating said NETS, utilizing said NETS to in vitro activate cytokine production from PBMC in vitro, and concentrating said cytokines. Cytokines generated by this methodology have superior ability to stimulate NK cells in vitro as compared to isolated NK stimulatory cytokines. The invention provides means of utilizing said symphony of cytokines to treat cancer and viral infections.

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