CA2209815A1 - Vaccine method using osmotic pump - Google Patents
Vaccine method using osmotic pumpInfo
- Publication number
- CA2209815A1 CA2209815A1 CA002209815A CA2209815A CA2209815A1 CA 2209815 A1 CA2209815 A1 CA 2209815A1 CA 002209815 A CA002209815 A CA 002209815A CA 2209815 A CA2209815 A CA 2209815A CA 2209815 A1 CA2209815 A1 CA 2209815A1
- Authority
- CA
- Canada
- Prior art keywords
- ctl
- antigen
- delivery
- osmotic pump
- need
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 229960005486 vaccine Drugs 0.000 title claims abstract description 17
- 230000003204 osmotic effect Effects 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 title claims description 14
- 239000000427 antigen Substances 0.000 claims abstract description 35
- 108091007433 antigens Proteins 0.000 claims abstract description 35
- 102000036639 antigens Human genes 0.000 claims abstract description 35
- 230000004044 response Effects 0.000 claims abstract description 24
- 238000013270 controlled release Methods 0.000 claims abstract description 7
- 230000005923 long-lasting effect Effects 0.000 claims abstract description 5
- 239000002671 adjuvant Substances 0.000 claims description 12
- 241000700605 Viruses Species 0.000 claims description 9
- 230000007503 antigenic stimulation Effects 0.000 claims description 7
- 230000003308 immunostimulating effect Effects 0.000 claims description 6
- 238000002347 injection Methods 0.000 claims description 4
- 239000007924 injection Substances 0.000 claims description 4
- 206010018691 Granuloma Diseases 0.000 claims description 3
- 229960001438 immunostimulant agent Drugs 0.000 claims description 3
- 239000003022 immunostimulating agent Substances 0.000 claims description 3
- 239000013612 plasmid Substances 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 231100000331 toxic Toxicity 0.000 claims description 2
- 230000002588 toxic effect Effects 0.000 claims description 2
- 230000001939 inductive effect Effects 0.000 abstract description 12
- 230000001472 cytotoxic effect Effects 0.000 abstract description 5
- 239000007943 implant Substances 0.000 abstract description 5
- 230000003389 potentiating effect Effects 0.000 abstract description 5
- 230000004913 activation Effects 0.000 abstract description 3
- 231100000433 cytotoxic Toxicity 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 230000036039 immunity Effects 0.000 description 7
- 230000006698 induction Effects 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 5
- 230000028993 immune response Effects 0.000 description 3
- 239000004005 microsphere Substances 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 108010041986 DNA Vaccines Proteins 0.000 description 2
- 229940021995 DNA vaccine Drugs 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000033687 granuloma formation Effects 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000004940 costimulation Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000000774 hypoallergenic effect Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Virology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
A vaccine protocol for inducing long-lasting cytotoxic T Iymphocyte (CTL) responses against specific antigen in humans involves use of a controlled release osmotic pump implant. Controlled release drives specific activation of CTL, facilitating continuous recirulation with potent cytotoxic activity for duration of implant.
Description
Abstract of the clisclQs~Jre A vaccine protocol for inducing long-lasting cytotoxic T Iymphocyte (CTL) responses against specific antigen in humans involves use of a col,llo"~d release osmotic pump implant. Controlled release drives specific activation of CTL, facilitating continuous recirulation with potent cytotoxic activity for duration of implant.
Os.-~otic pump vaccine for Cyt~t~,.ic T l~ ph~cytes The present invention relates to a method for vaccination that is particularly relevant for inducing immune responses to tumor cells and other agents that may benefit from potent and prolonged CTL responses. Although used for a variety of purposes, the method involves the use of a kind of system commonly termed controlled release. Various types of conl,olled release systems exist fordelivering pharmaceutical drugs or other pharmacologically active compounds.
Microspheres consisting of a polysaccharide matrix have also been used in the development of vaccines (1). The polymer microspheres have several disadvantages as a controlled release system, including residual toxic solvents in the microsphere preparation, less predictable release kinetics, and causing inflammation. These chemical spheres are also limited in terms of the kinds of materials they may contain, and are not suitable for live organisms or virus or for DNA expression systems. Moreover, the system is so far restricted to oral adminsitration to stimulate mucosal antibody (IgA) immunity (2).
The invention described herein relates to a method that offers several major advantages over existing methods used for vaccines designed to stimulate specific cell-mediated (Cytotoxic T Iymphocyte) immunity: (a) it provides for the use of a "mechanical antigen depot," circumventing the need for adjuvants that induce antigen depot effect via the induction of granulomatous lesions at the site of vaccine injection; (b) it provides a means for ongoing delivery of antigenic stimulation, a critical requirement for maintaining active CTL
responses, (c) it facilitates the induction of CTL immunity exclusively, withoutpromoting TH2-type antibody responses that tend to downregulate the strength of CTL responses; (d) it circumvents the need for immunostimulants, i.e. BCG, attenuated virus, as part of an adjuvant formulation, that pose significant risk of Vaccine method using Osmotic Purnp--Assignee: Millennium International Capital Investments, Inc.
CA 0220981~ 1997-07-10 systemic illness or infection; and (e) it facilitates the efficient and direct induction of CTL using class I restricted peptides, normally unable to induce responses because of their short half-lives in the body.
CTL are white blood cells found in the blood, spleen and Iymph. Their function is to destroy (1 ) virus-infected cells and (2) tumor cells that display tumor-associated antigen. After induction by antigen, i.e. immunization, a CTL
precursor cell (CTLp)will divide into daughter cells with the same antigenic specificity (i.e. pr~!;ferale), it will become a mature CTL, and will recirculate through the body with the ability to identify and destroy cells bearing the specific antigen. Recent data has shown that an active CTL immune response against a specific antigen requires continuous antigenic stimulation with that antigen (Kundig et al. 19g6). In the absence of antigen, once activated CTL
soon cease to recirculate through the body and find their way to the spleen.
Since CTL must deliver a lethal hit directly, their residence in the spleen precludes an active role in protection against infections or tumor growth at distant sites in the body (Kundig 1996).
CTL play a unique role in protecting against both a number of differentpathogens and tumors (4). The failure to induce effective CTL responses against pathogens or tumors can result in chronic disease. Consequently, significant eflort has been devoted towards developing vaccines that induce CTL responses against infectious agents or tumors. Despite the efforts, however, methods for inducing "active" CTL immunity have been slow in developing. Although it has been possible to induce transient CTL responses and to increase specific CTLp in the spleen, there has been no method described for inducing long-lived CTL responses (3). Nonetheless, there are situations, particularly in the case of tumors, which are notorious for their lack of immunogenicity, where long-lived CTL responses might have significant therapeutic value.
There is a fundamental reason why researchers have failed to induce long-lived CTL responses. For activation, CTL must be exposed to antigen in the context of MHC molecules on the surface of cells. However, once activated, CTL target the same antigen presenting cells for destruction. This paradoxical situation precludes the continuous antigenic stimulation necessary to maintain active CTL responses.
Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc.
CA 0220981~ 1997-07-10 Potent adjuvants have been used to cause wound (granuloma) formation, which entraps antigen and provides an antigen depot effect (5). In the process of causing granluomas formation, these adjuvants can cause serious lesions and systemic illness, including shock and death. Although the immunostimulatory effect is often regarded as an essential feature of the adjuvant, it is non-specific, typically resulting in the induction of so called TH2-type responses that interfere with strong CTL immunity. In addition to their toxicity, adjuvants have thus proved very inefficient at inducing strong and long lasting CTL responses.
Genetically engineered viruses modified to carry a gene encoding a specific antigen have been used as a vehicle for immunization. However, this method is intrinsically flawed, since clearance of the virus infection results in clearance of the antigen. The CTL inducing effect is therefore transient. Repeated injection with virus has been attempted, but this results in strong antibody responses against the virus, accelerating the speed by which the virus is cleared and further reducing the efficacy of the system.
DNA vaccines are also being developed for the purpose of inducing CTL
immunity. Once again, the system has intrinsic limitations that preclude its efficacy in inducing long-lasting CTL immunity. The DNA vaccines consist of a plasmid or similar genetic construct for expressing the antigen of interest. Up-take of theplasmid by cells of the body results in expression of the antigen and induction of CTL.As above, however, once cells expressing the construct have succeeded in inducing CTL, they are themselves targets for eradication by the CTL. The CTL
inducing effect is thus again transient.
Potent tumor specific CTL responses can be induced by vaccines. However, studies have shown that once the active CTL response has subsided, i.e. CTL
have stopped redrculating and have taken occupancy in the spleen, tumor cells can grow unopposed in the body (Unpublished results). Thus it is clearly critical for complete eradication and protection against resurgent tumor, that active CTLresponses are maintained for an extended period.
The "osmotic pump" controlled release device offers a means by which to provide ongoing antigenic stimulation. It is an inert mechanical device made of titaniumand is hypoallergenic. Thus it causes no significant irritation. Unlike adjuvants, Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc~
Antigenic Stimulation~CTL Response which create an antigen depot through stimulating ~ X
granuloma formation, the osmotic pump acts /' J
directly as a mechanical antigen depot. The device ,~
cannot be destroyed by CTL. Thus it goes on working to deliver antigen for the duration it is rime implanted in the skin (Figure 1). Importantly, our (a, recent findings have shown that the Osmotic Pump immunostimulatory effects of adjuvants may not be released Antigen needed when constant antigenic stimulation is ~ ~
present (6). Additionally, if antigen stimulation can ~ f~ Ongoing CTL
be directed to the appropriate environment, i.e.
Iymphoid organ, immunostimulants or costimulation can be circumvented (7); such Time control over antigen delivery is feasible using a (b) mechanical pump devivce for vaccine delivery. Figure 1. CTL response to Antigen Finally, since conventional adjuvants are not (a) Vaccines can only deliver specific antigen for a short time before the antigen required, i.e. to induce granuloma formation or is cleared by the body. Kinetics of the CTL response resembles the residual mmunosbmulatlon, the osmobc pump devlce can antigen profile.
be used to deliver only CTL-inducing formulations (b) Continuous delivery, whether involving rather than those that enhance competing TH2- an expression system such as a DNA
construct or a recombinant virus or type immune responses (8). organism delivering the target antigen, facilitates an ongoing CTL response for the duration of implant of the delivery C~t~o~i.. c.~t~ ~ th~ h~ ~. Wlli~h .. - system. (Residual antigen: black line E*ehlsive F~ or F~i~d ,e i9 CI~H..e~ ~r~ Active CTL response: red line) E~ as follow~:
1. UX of e~tF~."~ rclc~c implantablc "oomotic pump" dcvicc f~r c~ntinuou~ do~ivory of ~ntigcn or ~ntig~n cxprcs~.on sy~u,~, ~uch ~s D~/\ con~truct~ inehding pl~mid~, recombin~nt virux~ nd rccomb.n~nt ~ry~Ri3ll,s.
Os.-~otic pump vaccine for Cyt~t~,.ic T l~ ph~cytes The present invention relates to a method for vaccination that is particularly relevant for inducing immune responses to tumor cells and other agents that may benefit from potent and prolonged CTL responses. Although used for a variety of purposes, the method involves the use of a kind of system commonly termed controlled release. Various types of conl,olled release systems exist fordelivering pharmaceutical drugs or other pharmacologically active compounds.
Microspheres consisting of a polysaccharide matrix have also been used in the development of vaccines (1). The polymer microspheres have several disadvantages as a controlled release system, including residual toxic solvents in the microsphere preparation, less predictable release kinetics, and causing inflammation. These chemical spheres are also limited in terms of the kinds of materials they may contain, and are not suitable for live organisms or virus or for DNA expression systems. Moreover, the system is so far restricted to oral adminsitration to stimulate mucosal antibody (IgA) immunity (2).
The invention described herein relates to a method that offers several major advantages over existing methods used for vaccines designed to stimulate specific cell-mediated (Cytotoxic T Iymphocyte) immunity: (a) it provides for the use of a "mechanical antigen depot," circumventing the need for adjuvants that induce antigen depot effect via the induction of granulomatous lesions at the site of vaccine injection; (b) it provides a means for ongoing delivery of antigenic stimulation, a critical requirement for maintaining active CTL
responses, (c) it facilitates the induction of CTL immunity exclusively, withoutpromoting TH2-type antibody responses that tend to downregulate the strength of CTL responses; (d) it circumvents the need for immunostimulants, i.e. BCG, attenuated virus, as part of an adjuvant formulation, that pose significant risk of Vaccine method using Osmotic Purnp--Assignee: Millennium International Capital Investments, Inc.
CA 0220981~ 1997-07-10 systemic illness or infection; and (e) it facilitates the efficient and direct induction of CTL using class I restricted peptides, normally unable to induce responses because of their short half-lives in the body.
CTL are white blood cells found in the blood, spleen and Iymph. Their function is to destroy (1 ) virus-infected cells and (2) tumor cells that display tumor-associated antigen. After induction by antigen, i.e. immunization, a CTL
precursor cell (CTLp)will divide into daughter cells with the same antigenic specificity (i.e. pr~!;ferale), it will become a mature CTL, and will recirculate through the body with the ability to identify and destroy cells bearing the specific antigen. Recent data has shown that an active CTL immune response against a specific antigen requires continuous antigenic stimulation with that antigen (Kundig et al. 19g6). In the absence of antigen, once activated CTL
soon cease to recirculate through the body and find their way to the spleen.
Since CTL must deliver a lethal hit directly, their residence in the spleen precludes an active role in protection against infections or tumor growth at distant sites in the body (Kundig 1996).
CTL play a unique role in protecting against both a number of differentpathogens and tumors (4). The failure to induce effective CTL responses against pathogens or tumors can result in chronic disease. Consequently, significant eflort has been devoted towards developing vaccines that induce CTL responses against infectious agents or tumors. Despite the efforts, however, methods for inducing "active" CTL immunity have been slow in developing. Although it has been possible to induce transient CTL responses and to increase specific CTLp in the spleen, there has been no method described for inducing long-lived CTL responses (3). Nonetheless, there are situations, particularly in the case of tumors, which are notorious for their lack of immunogenicity, where long-lived CTL responses might have significant therapeutic value.
There is a fundamental reason why researchers have failed to induce long-lived CTL responses. For activation, CTL must be exposed to antigen in the context of MHC molecules on the surface of cells. However, once activated, CTL target the same antigen presenting cells for destruction. This paradoxical situation precludes the continuous antigenic stimulation necessary to maintain active CTL responses.
Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc.
CA 0220981~ 1997-07-10 Potent adjuvants have been used to cause wound (granuloma) formation, which entraps antigen and provides an antigen depot effect (5). In the process of causing granluomas formation, these adjuvants can cause serious lesions and systemic illness, including shock and death. Although the immunostimulatory effect is often regarded as an essential feature of the adjuvant, it is non-specific, typically resulting in the induction of so called TH2-type responses that interfere with strong CTL immunity. In addition to their toxicity, adjuvants have thus proved very inefficient at inducing strong and long lasting CTL responses.
Genetically engineered viruses modified to carry a gene encoding a specific antigen have been used as a vehicle for immunization. However, this method is intrinsically flawed, since clearance of the virus infection results in clearance of the antigen. The CTL inducing effect is therefore transient. Repeated injection with virus has been attempted, but this results in strong antibody responses against the virus, accelerating the speed by which the virus is cleared and further reducing the efficacy of the system.
DNA vaccines are also being developed for the purpose of inducing CTL
immunity. Once again, the system has intrinsic limitations that preclude its efficacy in inducing long-lasting CTL immunity. The DNA vaccines consist of a plasmid or similar genetic construct for expressing the antigen of interest. Up-take of theplasmid by cells of the body results in expression of the antigen and induction of CTL.As above, however, once cells expressing the construct have succeeded in inducing CTL, they are themselves targets for eradication by the CTL. The CTL
inducing effect is thus again transient.
Potent tumor specific CTL responses can be induced by vaccines. However, studies have shown that once the active CTL response has subsided, i.e. CTL
have stopped redrculating and have taken occupancy in the spleen, tumor cells can grow unopposed in the body (Unpublished results). Thus it is clearly critical for complete eradication and protection against resurgent tumor, that active CTLresponses are maintained for an extended period.
The "osmotic pump" controlled release device offers a means by which to provide ongoing antigenic stimulation. It is an inert mechanical device made of titaniumand is hypoallergenic. Thus it causes no significant irritation. Unlike adjuvants, Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc~
Antigenic Stimulation~CTL Response which create an antigen depot through stimulating ~ X
granuloma formation, the osmotic pump acts /' J
directly as a mechanical antigen depot. The device ,~
cannot be destroyed by CTL. Thus it goes on working to deliver antigen for the duration it is rime implanted in the skin (Figure 1). Importantly, our (a, recent findings have shown that the Osmotic Pump immunostimulatory effects of adjuvants may not be released Antigen needed when constant antigenic stimulation is ~ ~
present (6). Additionally, if antigen stimulation can ~ f~ Ongoing CTL
be directed to the appropriate environment, i.e.
Iymphoid organ, immunostimulants or costimulation can be circumvented (7); such Time control over antigen delivery is feasible using a (b) mechanical pump devivce for vaccine delivery. Figure 1. CTL response to Antigen Finally, since conventional adjuvants are not (a) Vaccines can only deliver specific antigen for a short time before the antigen required, i.e. to induce granuloma formation or is cleared by the body. Kinetics of the CTL response resembles the residual mmunosbmulatlon, the osmobc pump devlce can antigen profile.
be used to deliver only CTL-inducing formulations (b) Continuous delivery, whether involving rather than those that enhance competing TH2- an expression system such as a DNA
construct or a recombinant virus or type immune responses (8). organism delivering the target antigen, facilitates an ongoing CTL response for the duration of implant of the delivery C~t~o~i.. c.~t~ ~ th~ h~ ~. Wlli~h .. - system. (Residual antigen: black line E*ehlsive F~ or F~i~d ,e i9 CI~H..e~ ~r~ Active CTL response: red line) E~ as follow~:
1. UX of e~tF~."~ rclc~c implantablc "oomotic pump" dcvicc f~r c~ntinuou~ do~ivory of ~ntigcn or ~ntig~n cxprcs~.on sy~u,~, ~uch ~s D~/\ con~truct~ inehding pl~mid~, recombin~nt virux~ nd rccomb.n~nt ~ry~Ri3ll,s.
2~ ~aid d~X ~ery ~ claimcd in 1, to providc long la3ting antigcnic 3timul~tion ~nd ong~ rccirculation of CTL. Thc CTL rc3ponx can bc m~int~incd for period of 12 month~ comparcd to ourrcnt mcthod3 that inducc rc~ponoc for only about 2 ~ e.
Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc.
Vaccine method using Osmotic Pump--Assignee: Millennium International Capital Investments, Inc.
Claims (5)
1. Use of controlled release implantable "osmotic pump" device for continuous delivery of antigen or antigen expression systems, such as DNA constructs including plasmids, recombinant viruses, and recombinant organisms.
2. Said delivery as claimed in 1, to provide long-lasting antigenic stimulation and ongoing recirculation of CTL. The CTL response can be maintained for a period of 12 months compared to current methods that induce response for only about 2 weeks.
3. Said delivery as claimed in 1, as a mechanical antigen depot. This replaces need for adjuvants that cause indirect antigen depot through stimulating body toinduce granulomatous lesions at site of vaccine injection.
4. Said delivery as claimed in 1, acts as "constant injector," avoiding the need for repeated injection of expression-type vaccines, such as DNA constructs or recombinant virus designed to express target antigen, in order to increase the frequency of antigen-specific CTL.
5. Said delivery as claimed in 1, acts as a mechanical adjuvant that provides constant CTL immunostimulation, circumventing the need for highly toxic adjuvants used as immunostimulants.
Priority Applications (22)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002209815A CA2209815A1 (en) | 1997-07-10 | 1997-07-10 | Vaccine method using osmotic pump |
| IL13391298A IL133912A0 (en) | 1997-07-10 | 1998-07-10 | A method of inducing ctl response |
| NZ502168A NZ502168A (en) | 1997-07-10 | 1998-07-10 | Inducing and maintaining a CTL response by delivering antigen to the lymphatic system of a mammal via an external apparatus |
| JP2000501773A JP3857877B2 (en) | 1997-07-10 | 1998-07-10 | Method for inducing a CTL response |
| EP06113679.2A EP1787654B1 (en) | 1997-07-10 | 1998-07-10 | Intralymphatic immunization for inducing sustained effector CTL responses |
| PT98936827T PT1003548E (en) | 1997-07-10 | 1998-07-10 | DEVICE FOR THE INDUCTION OF A CTL RESPONSE |
| ES06113679.2T ES2438735T3 (en) | 1997-07-10 | 1998-07-10 | Intra-lymphatic immunization to induce prolonged effector CTL responses |
| AT98936827T ATE325619T1 (en) | 1997-07-10 | 1998-07-10 | DEVICE FOR INDUCING A CTL RESPONSE |
| PCT/US1998/014289 WO1999002183A2 (en) | 1997-07-10 | 1998-07-10 | A method of inducing a ctl response |
| CA002295964A CA2295964A1 (en) | 1997-07-10 | 1998-07-10 | A method of inducing a ctl response |
| EP10178583A EP2286831A1 (en) | 1997-07-10 | 1998-07-10 | A method of inducing a CTL response |
| AU85689/98A AU739189B2 (en) | 1997-07-10 | 1998-07-10 | A method of inducing a CTL response |
| ES98936827T ES2265165T3 (en) | 1997-07-10 | 1998-07-10 | DEVICE TO INDUCE AN ANSWER LTC. |
| DE69834494T DE69834494T2 (en) | 1997-07-10 | 1998-07-10 | DEVICE FOR INDUCING A CTL RESPONSE |
| EP98936827A EP1003548B1 (en) | 1997-07-10 | 1998-07-10 | Device for inducing a ctl response |
| US09/380,534 US6994851B1 (en) | 1997-07-10 | 1998-07-10 | Method of inducing a CTL response |
| IL133912A IL133912A (en) | 1997-07-10 | 2000-01-06 | Use of an antigen in the preparation of a composition for inducing an effector cytotoxic t lymphocyte (ctl) response |
| US09/776,232 US6977074B2 (en) | 1997-07-10 | 2001-02-02 | Method of inducing a CTL response |
| US11/313,152 US7364729B2 (en) | 1997-07-10 | 2005-12-19 | Method of inducing a CTL response |
| US11/418,397 US8372393B2 (en) | 1997-07-10 | 2006-05-03 | Method of inducing a CTL response |
| US11/418,497 US20090035252A1 (en) | 1997-07-10 | 2006-05-03 | Method of inducing a CTL response |
| IL181687A IL181687A0 (en) | 1997-07-10 | 2007-03-01 | A method of inducing a ctl response |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002209815A CA2209815A1 (en) | 1997-07-10 | 1997-07-10 | Vaccine method using osmotic pump |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2209815A1 true CA2209815A1 (en) | 1999-01-10 |
Family
ID=29274862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002209815A Abandoned CA2209815A1 (en) | 1997-07-10 | 1997-07-10 | Vaccine method using osmotic pump |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2209815A1 (en) |
-
1997
- 1997-07-10 CA CA002209815A patent/CA2209815A1/en not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |