A low-cost topical immunotherapy formulation suitable for treating cervical cancer in low and middle income countries and low-resource settings in the U.S.
一种低成本局部免疫治疗制剂,适用于低收入和中等收入国家以及美国资源匮乏地区的宫颈癌治疗。
基本信息
- 批准号:10252242
- 负责人:
- 金额:$ 40万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsAnimal ModelAnimalsAntigen-Presenting CellsAntigensAreaB-LymphocytesBacterial AntigensBiodistributionCarcinomaCell SurvivalCell surfaceCellsCervicalCervical dysplasiaCessation of lifeClinic VisitsClinical DataClinical TrialsCold ChainsCommunity HospitalsComplexCreamCutaneous MelanomaDNA MaintenanceDataDisease ProgressionEarly treatmentEnvironmentEpidemiologyEpitope spreadingEpitopesEquilibriumEquipmentEvaluationExcipientsFamilyFemaleFormulationFutureGoalsHumanHuman PapillomavirusHuman papillomavirus 16ImageImmune responseImmunityImmunohistochemistryImmunologyImmunomodulatorsImmunotherapeutic agentImmunotherapyIn VitroInfrastructureInnate Immune ResponseIntralesional InjectionsInvestigationInvestigational New Drug ApplicationLuciferasesMalignant NeoplasmsMalignant neoplasm of cervix uteriMerkel cell carcinomaMethodsModelingMonitorMorphogenesisMusPerformancePharmaceutical PreparationsPharmacologyPhasePositioning AttributeProbabilityPrognosisQuality ControlResearch PersonnelResourcesSafetySelf AdministrationSerious Adverse EventSmall Business Innovation Research GrantSouth AfricaSpecialistSuperhelical DNASupportive careT-Cell ActivationTemperatureTestingTherapeuticTissuesTrainingTransfectionTransgenic OrganismsUnderserved PopulationVaginaViscosityVulvar Squamous Cell CarcinomaWomanadaptive immune responseanimal imagingbarrier to carebasecancer immunotherapycancer typecervicovaginalcostenhanced green fluorescent proteinfallsfertility preservationimaging studyimmune activationimprovedin vivoinnovationlow and middle-income countriesmouse modelneoplastic cellplasmid DNApre-clinicalproduct developmentprotein expressionreproductiveskin squamous cell carcinomasuccesstime usetumoruptake
项目摘要
The goal of this project is to deliver an affordable immunotherapy to treat advanced cervical cancer in low-
and middle-income countries (LMICs) and low-resource settings in the U.S. A longer-term goal is to treat earlier
stages of cervical dysplasia and assess immunity to the causative agent, human papillomavirus (HPV). The
heavy burden of suffering and death from cervical cancer disproportionately falls on women in resource poor
settings. Overcoming barriers to treatment, i.e. lack of infrastructure, trained specialists, specialized equipment,
cold chain, and financial resources, requires a paradigm shift in the approach to treatment that can be achieved
by the innovative immunotherapeutic agent proposed here.
IFx-Hu2.1 (SN63/016,700) is a cream-based therapeutic immunomodulator that will be optimized for stability and
performance. Our IFx-Hu2 family contains a plasmid DNA (pDNA) bulk drug substance, which can be produced
for a fraction of the cost of current immunotherapies. The pDNA encodes a complex bacterial antigen, Emm55.
When expressed on the tumor cell surface, Emm55 attracts antigen presenting cells and other cells of the innate
immune response. Non-self-epitopes such as tumor and HPV antigens are then exposed in such a way as to set
up multi-antigenic cellular and humoral adaptive immune responses. Emm55-based therapies induce
personalized, multivalent, systemic, and sustained immune responses and have the potential to treat a
broad range of cancers through enhanced tumor recognition, immune activation and epitope spreading.
Intralesional injection of IFx-Hu2.0 has an established safety profile in multiple animal studies and is currently
being tested in Phase 1 human clinical trials for cutaneous melanoma, Merkel cell carcinoma and cutaneous
squamous cell carcinoma. Our preliminary clinical data corroborate pre-clinical observations, showing the
activation of T- and B-cell immune responses and tumor reduction, with no short or long-term adverse effects.
We propose to optimize the IFx-Hu2.1 formulation for temperature stability using established methods and
models. In vitro evaluation, to include standard quality control methods and a human vaginal epithelium
carcinoma model, will be followed by in vivo uptake, expression, and disease progression studies in a mouse
model of cervical cancer. Room temperature storage and self-administration will circumvent onerous clinic visits,
improve prognosis and preserve fertility. IFx-Hu2.1 cream formulation will provide a non-toxic cancer
therapeutic treatment with minimal supportive care requirements, featuring unique delivery, and high
applicability/impact to underserved populations. The data obtained by completing these studies will position
Morphogenesis, Inc. to submit an Investigational New Drug application to conduct a clinical trial for women in a
local community hospital (low-resource setting) and in South Africa (LMIC). These trials will be the objective of
an SBIR Phase 2 proposal.
这个项目的目标是提供一种负担得起的免疫疗法来治疗晚期宫颈癌
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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Michael J Shamblott其他文献
Michael J Shamblott的其他文献
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{{ truncateString('Michael J Shamblott', 18)}}的其他基金
GENES AND GENE TARGETS FROM THE DOWN SYNDROME REGION
唐氏综合症区域的基因和基因靶点
- 批准号:
2655096 - 财政年份:1998
- 资助金额:
$ 40万 - 项目类别:
GENES AND GENE TARGETS FROM THE DOWN SYNDROME REGION
唐氏综合症区域的基因和基因靶点
- 批准号:
2332229 - 财政年份:1997
- 资助金额:
$ 40万 - 项目类别:
GENES AND GENE TARGETS FROM THE DOWN SYNDROME REGION
唐氏综合症区域的基因和基因靶点
- 批准号:
2196531 - 财政年份:1996
- 资助金额:
$ 40万 - 项目类别:
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