Compositions, devices and methods for inducing immune responses to infectious agents
AssigneeSigilon Therapeutics, Inc.
InventorsHozefa Bandukwala, David E. Moller, David Peritt
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Abstract
Described herein are implantable devices comprising cells engineered to express and secrete antigens of infectious agents. The devices are useful for inducing protective immune responses against infectious agents.
Claims22
An implantable device for inducing a protective immune response to an infectious agent, the device comprising a first antigen-expressing cell that is engineered to express and secrete a first antigen of the infectious agent, wherein the device is configured to exhibit the following properties when implanted into a subject:
- (a) an immune cell of the subject does not contact the first antigen-expressing cell;
- (b) the first antigen-expressing cell does not exit the device;
- and
- (c) continuous delivery of the first antigen to the subject in an amount and for a time period effective to elicit the protective immune response, and wherein the device comprises at least one of the following features:
- (i) the first antigen-expressing cell is engineered to express and secrete at least two, three or more different antigens of the infectious agent;
- (ii) the device comprises a second antigen-expressing cell that is engineered to express and secrete a second antigen of the infectious agent;
- (iii) the device comprises a third antigen-expressing cell that is engineered to express and secrete a third antigen of the infectious agent that is different than each antigen secreted by the first antigen-expressing cell and the antigen-expressing second cell;
- (iv) the device is configured to deliver to the subject an immunomodulatory agent that enhances the protective immune response to the infectious agent;
- (v) the first antigen comprises a secretory signal peptide sequence of MGWRAAGALLLALLLHGRLLA (SEQ ID NO:
- 1);
- (vi) a foreign body response (FBR) mitigating compound is disposed on the surface of the device;
- and,
- (vii) the surface of the device does not contain alginate.
A hydrogel capsule comprising:
- (a) a cell-containing compartment which comprises living cells encapsulated in a first polymer composition, wherein the living cells are engineered to continuously express and secrete a first antigen of an infectious agent;
- and
- (b) a barrier compartment surrounding the cell-containing compartment and comprising a second polymer composition which comprises an alginate covalently modified with a compound selected from the group consisting of
- or a pharmaceutically acceptable salt of the compound,
- wherein the hydrogel capsule has a spherical shape and has a diameter of 0.5 millimeter to 5 millimeters.
A method of inducing a neutralizing antibody (NAb) response to an infectious agent comprising implanting into a subject a device comprising a first antigen-expressing cell that is engineered to express and secrete a first antigen of the infectious agent, wherein the device is configured to exhibit the following properties when implanted into a subject:
- (a) an immune cell of the subject does not contact the first antigen-expressing cell;
- (b) the first antigen-expressing cell does not exit the device;
- and
- (c) delivery of the first secreted antigen to the subject in an amount and for a time period effective to elicit the protective immune response, and wherein the device comprises at least one of the following features;
- (i) the device comprises a second antigen-expressing cell that is engineered to express and secrete a second antigen of the infectious agent;
- (ii) the device comprises a third antigen-expressing cell that is engineered to express and secrete a third antigen of the infectious agent;
- (iii) the device is configured to continuously deliver to the subject throughout the time period an immunomodulatory agent that enhances the protective immune response to the infectious agent;
- (iv) the first secreted antigen comprises a secretory signal peptide sequence of MGWRAAGALLLALLLHGRLLA (SEQ ID NO:1);
- (v) a compound or polymer disposed on the surface of the device that mitigates the foreign body response (FBR) to the device;
- and
- (vi) the surface of the device does not contain alginate.
Dependencies are inferred from the claim text.