Pdl1 peptides for use in cancer vaccines

a cancer vaccine and peptide technology, applied in the field of pdl1 peptide fragments, can solve the problems of malignant cancer, poor prognosis for affected individuals, and the inability of the immune system to respond effectively to these antigens

Inactive Publication Date: 2020-10-29
IO BIOTECH APS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0079]FIG. 11. Vaccination with mPD-L1long1 shows anti-tumor effect in mice. A) shows the timeline for the experiment described in Example 6; B) Change in tumor volume over time for each mouse (M1-M3 vaccinated with Montanide only; M4-M5 vaccinated with mPD-L1long1 plus Montanide); C) Kaplan-Meier survival curve; D) Change in mean tumor volume over time for each group. n=3 mice / group.

Problems solved by technology

The immune system has the capacity to recognize and destroy neoplastic cells; nevertheless, despite the fact that neoplastic transformation is associated with the expression of immunogenic antigens, the immune system often fails to respond effectively to these antigens.
When this happens, the neoplastic cells proliferate uncontrollably leading to the formation of malignant cancers with poor prognosis for the affected individuals.
However, although many DC vaccination trials have been conducted, clinical benefit has been limited for the majority of patients.
However, the clinical benefits were limited and immunological monitoring of the patients revealed that their peripheral blood mononuclear cells (PBMCs) had only limited reactivity toward DCvacc.

Method used

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  • Pdl1 peptides for use in cancer vaccines
  • Pdl1 peptides for use in cancer vaccines
  • Pdl1 peptides for use in cancer vaccines

Examples

Experimental program
Comparison scheme
Effect test

example 1

Materials and Methods

[0223]Patients and Donors 26 stage IV melanoma patients were enrolled in an open-labeled, non-randomized phase I / II study (EudraCT number 2009-010194-20; Clinicaltrials.gov identifier: NCT00978913). The protocol was approved by the Scientific Ethics Committee for The Capital Region of Denmark (H-A-2009-013), the Danish Medicines Agency (2612-4030), the Danish Data Protection Agency and conducted in accordance with the provisions of the Declaration of Helsinki. Written informed consent from the patients was obtained before study entry. The clinical and immunological results will be reported elsewhere (Borch et al., in preparation). In short patients were injected with autologous DC vaccines intradermally fortnightly six times and subsequently every four weeks until progression. Concomitantly, patients were treated with a metronomic cyclophosphamide regimen (50 mg twice a day) biweekly.

[0224]For immune monitoring purposes Peripheral Blood Mononuclear Cells (PBMC) ...

example 2

Spontanous Immune Responses Against IO104.1 in Human Patients

[0243]We first analysed the immune responses against two versions of IO104.1 in Tumor infiltrating T cells from melanoma patients. Next we analysed if PDL111 specific T cells were able to recognize IO104.1

Materials and Methods

Peptides

[0244]

(minimal epitope - SEQ ID NO: 92)PDL111 = CLGVALTFI(SEQ ID NO: 92)IO104 (PDLong2) = VILGAILLCLGVALTFIFRLRKG(SEQ ID NO: 52)IO104.1-OH = Arg-Thr-His-Leu-Val-Ile-Leu-Gly-Ala-Ile-Leu-Leu-Cys-Leu-Gly-Val-Ala-Leu-Thr-Phe-Ile-Phe-Arg-Leu-Arg-Lys-Gly-Arg-OH (C-terminus acid)(SEQ ID NO: 52 with C terminal amide)IO104.1-NH2 = Arg-Thr-His-Leu-Val-Ile-Leu-Gly-Ala-Ile-Leu-Leu-Cys-Leu-Gly-Val-Ala-Leu-Thr-Phe-Ile-Phe-Arg-Leu-Arg-Lys-Gly-Arg-NH2 (C-terminus amide)

ELISPOT Assay

[0245]The ELISPOT technique enabled screening a high number of peptide antigens for T-cell recognition, despite the availability of relatively few T-cells. We used the ELISPOT assay to quantify peptide-specific, effector cells that...

example 3

PDL1 Specific T Cells are Naturally Occurring in Mice

[0249]We hypothesized that if PD-L1 specific T cells are natural occurring, they should activate and expand in response to inflammation.

Materials and Methods

[0250]C56BL / 6 mice were injected with 1 μg IFNγ in 200 μl PBS i.p (or no injection for control) two days apart (day 0+2) to simulate inflammation. On day 5 the mice were sacrificed and a single cell solution of the removed spleen was made for further analysis by IFNγ-Elispot.

[0251]9×105 splenocytes / well were stimulated ex vivo in Elispot plates with 5 μg / ml peptides from murine (m)PDL1 for 18-20 hours. Spot count for the peptide stimulated wells was subtracted the background (spot count of wells with no peptide stimulation).

[0252]The peptides from PDL1 were selected based on the following reasoning.

[0253]The Sequence of mPD-L1 is:

(SEQ ID NO: 95 - N-terminal / signal sequence inbold, C-terminal / membrane-spanning regionunderlined)MRIFAGIIFT ACCHLLRAFT ITAPKDLYVV EYGSNVTMECRFPVEREL...

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Abstract

The present invention relates to a PD-L1 peptide fragment, useful in cancer therapies as well as PD-L1 peptide fragments for use in a method for treatment or prevention of a cancer, when administered simultaneously or sequentially with an additional cancer therapy.

Description

TECHNICAL FIELD[0001]The present invention relates to novel PD-L1 peptide fragments, as well as compositions, uses, and kit-of-parts comprising these peptide fragments. Furthermore, the invention concerns PD-L1 peptide fragments for use in a method for treatment or prevention of a cancer, when administered simultaneously or sequentially with an additional cancer therapy.BACKGROUND ART[0002]The immune system has the capacity to recognize and destroy neoplastic cells; nevertheless, despite the fact that neoplastic transformation is associated with the expression of immunogenic antigens, the immune system often fails to respond effectively to these antigens. The immune system becomes tolerant towards these antigens. When this happens, the neoplastic cells proliferate uncontrollably leading to the formation of malignant cancers with poor prognosis for the affected individuals. The acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Several lines of evidence...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/705A61K39/395A61P35/00A61K45/06
CPCA61K2039/545A61K2039/55511A61K39/3955A61P35/00A61K2039/572A61K45/06C07K14/70596A61K38/00C07K14/705A61P31/04A61P31/12A61P33/06A61P37/04A61P37/06Y02A50/30
Inventor ANDERSEN, MADS HALD
Owner IO BIOTECH APS
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