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Recombinant listeria vaccine strains and methods of using the same in cancer immunotherapy

A Listeria monocytogenes strain technology, applied in the field of recombinant Listeria monocytogenes vaccine strains and its use in cancer immunotherapy, can solve toxicity and other problems

Inactive Publication Date: 2018-08-03
ADVAXIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most patients with HPVOPC are at an advanced stage, and standard chemotherapy regimens can lead to severe toxicity
Thus, patients with favorable prognosis are paradoxically at higher risk for treatment-related long-term adverse quality-of-life outcomes

Method used

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  • Recombinant listeria vaccine strains and methods of using the same in cancer immunotherapy
  • Recombinant listeria vaccine strains and methods of using the same in cancer immunotherapy
  • Recombinant listeria vaccine strains and methods of using the same in cancer immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0240] Example 1: LLO-antigen fusions induce anti-tumor immunity

Embodiment 1-2

[0242] cell line

[0243] C57BL / 6 syngeneic TC-1 tumors were immortalized with HPV-16 E6 and E7 and transformed with the c-Ha-ras oncogene. T.C. Wu (Johns Hopkins University School of Medicine, Baltimore, MD) disclosed that TC-1 is a highly tumorigenic lung epithelial cell that expresses low levels of HPV-16 E6 and E7 and is transformed by the c-Ha-ras oncogene . Keep TC-1 at 37°C and 10% CO 2 Grow in RPMI1640, 10% FCS, 2mM L-glutamine, 100U / ml penicillin, 100μg / ml streptomycin, 100μM non-essential amino acids, 1mM sodium pyruvate, 50 micromolar (mcM) 2-ME, 400μg (mcg) / mlG418 and 10% National Collection Type Culture-109 medium (National Collection Type Culture-109 medium). C3 are mouse embryonic cells from C57BL / 6 mice immortalized with the complete HPV 16 genome and transformed with pEJ-ras. EL-4 / E7 is thymoma EL-4 transduced with E7 retrovirus.

[0244] Listeria monocytogenes strains and reproduction

[0245] The Listeria bacterial strain used is Lm-LLO-E7 (hly-E7 fusi...

Embodiment 2

[0266] Example 2: LM-LLO-E7 Treatment Causes Proliferation of TC-1 Specific Splenocytes

[0267] To measure the induction of T cells by Lm-E7 with Lm-LLO-E7, TC-1 specific proliferative responses (a measure of antigen-specific immune activity) were measured in immunized mice. Splenocytes from mice immunized with Lm-LLO-E7 were exposed to irradiated TC-1 cells at splenocyte:TC-1 ratios of 20:1, 40:1, 80:1, and 160:1 (as Proliferation occurs when the source of E7) ( Figure 4 ). In contrast, splenocytes from mice immunized with Lm-E7 and rLm controls showed only background levels of proliferation.

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Abstract

The present invention provides methods of treating, protecting against, and inducing an immune response against a human papillomavirus-associated tumor or cancer, comprising the step of administeringto a subject a recombinant Listeria strain expressing a construct comprising at least one human papillomavirus antigen.

Description

technical field [0001] The present invention provides methods of treating, protecting against, and inducing an immune response to human papillomavirus-associated tumors or cancers, the methods comprising administering to a subject a drug expressing a drug comprising at least one human papillomavirus antigen Steps for constructing recombinant Listeria strains. Background technique [0002] Human papillomavirus (HPV)-associated oropharyngeal cancer (HPVOPC) is increasingly prevalent in the United States (225% increase from 1988 to 2004). HPVOPC patients tended to be younger and had a good prognosis, with a 69% lower risk of death compared with HPV-negative patients. However, most HPVOPC patients are at an advanced stage, and standard chemotherapy regimens can lead to severe toxicity. Thus, patients with a favorable prognosis are paradoxically at higher risk for treatment-related long-term adverse quality-of-life outcomes. Immunotherapy has the potential to reduce toxicity b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/74C07K14/005C07K14/195A61K39/02A61K39/12A61K39/39A61K39/00
CPCA61K39/02A61K39/12C07K14/195C07K2319/55C12N2710/20034C12N2710/20022A61P35/00A61K39/0011A61K39/0208A61K39/39C07K14/005C12N15/74A61K2039/545C07K2319/21A61K35/74A61K39/245A61K2039/572
Inventor R·珀蒂K·佩里
Owner ADVAXIS
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