WO2014090265A1 - Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer - Google Patents

Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer Download PDF

Info

Publication number
WO2014090265A1
WO2014090265A1 PCT/EP2012/005154 EP2012005154W WO2014090265A1 WO 2014090265 A1 WO2014090265 A1 WO 2014090265A1 EP 2012005154 W EP2012005154 W EP 2012005154W WO 2014090265 A1 WO2014090265 A1 WO 2014090265A1
Authority
WO
WIPO (PCT)
Prior art keywords
fsp
vaccine
cancer
msi
tumor
Prior art date
Application number
PCT/EP2012/005154
Other languages
English (en)
French (fr)
Inventor
Matthias Kloor
Miriam Reuschenbach
Magnus Von Knebel-Doeberitz
Original Assignee
Ruprecht-Karls-Universität Heidelberg
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ruprecht-Karls-Universität Heidelberg filed Critical Ruprecht-Karls-Universität Heidelberg
Priority to BR112015013737-7A priority Critical patent/BR112015013737B1/pt
Priority to RU2015115785A priority patent/RU2644677C2/ru
Priority to KR1020157015802A priority patent/KR101810840B1/ko
Priority to PCT/EP2012/005154 priority patent/WO2014090265A1/en
Priority to CN201280077683.XA priority patent/CN104853764B/zh
Publication of WO2014090265A1 publication Critical patent/WO2014090265A1/en

Links

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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention provides a vaccine for prevention and treatment of cancer characterized by microsatellite instability (MSI) .
  • the vaccine contains an MSI-specific frameshift peptide (FSP) generating humoral and cellular responses against tumor cells or a nucleic acid encoding said FSP.
  • MSI-specific frameshift peptide FSP
  • MSI microsatellite instability
  • MSI colorectal cancers are characterized by a high immunogenicity that results from the generation of numerous frameshift peptides (FSP) during the development of MSI tumors as a direct result of mismatch repair deficiency leading to alterations of the translational reading frame when microsatellites in gene-encoding regions are affected by mutation ( Figure 1) .
  • FSP frameshift peptides
  • Figure 1 The abundance of predictable MSI-specific FSP antigens and the fact that they directly result from the malignant transformation process render FSP highly promising targets for immune therapy.
  • the human immune system is a potential resource to eradicate tumor cells and that effective treatment can be developed if the components of the immune system are properly stimulated to recognize and eliminate cancer cells.
  • immunotherapy which comprises compositions and methods to activate the body's immune system, either directly or indirectly, to shrink or eradicate cancer, has been studied for many years as an adjunct to conventional cancer therapy.
  • T-cells For most T-cells, production of IL-2 and proliferation require a co- stimulatory signal simultaneous with TCR engagement, otherwise, T-cells may enter a functionally unresponsive state, known as clonal anergy.
  • HNPCC hereditary non-polyposis colorectal cancer
  • FSP Frameshift peptides
  • FSP vaccination has been designed for therapy of 15% of colon cancers and tumors of the endometrium, stomach, small intestine and other organs;
  • FSP vaccination may be used as a preventive vaccination in high risk groups.
  • Figure 1 Schematic illustration of coding microsatellite instability resulting from DNA mismatch repair deficiency (Kloor et al., 2010)
  • Truncated proteins encompassing FSP sequences are generated when coding microsatellite mutations lead to alterations of the translational reading frame (example: TGFBR2 protein) .
  • FIG. 1 Exemplary T cell responses against newly designed FSPs in peripheral blood from three patients with MSI colon cancer
  • FIG. 3 Humoral immune responses against FSPs derived from AIM2 (-1) , HTOOl(-l), TAFlB(-l), and TGFBR2 (-1 ) ELISA revealed FSP-specific antibody responses directed against neopeptides derived from AI 2(-1), HTOOl(-l), TAFlB(-l), and TGFBR2 (-1 ) . Peptide specificity was demonstrated by preabsorption of respective serum antibodies as described previously (Reuschenbach et al., 2008) .
  • the present invention provides a vaccine containing an MSI tumor specific frameshift peptide (FSP), e.g., derived from TAF1B (Acc.No. L39061) , HT001 (Acc.No. AF113539), AIM2 (Acc.No. AF024714), or TGFBR2 (Acc.No. NM_003242) or a nucleic acid encoding said FSP wherein said FSP is capable of eliciting an immune response against cancer showing MSI.
  • FSP tumor specific frameshift peptide
  • the vaccine of the present invention contains
  • an FSP comprising or consisting of the following amino acid sequence: NTQIKALNRGLKKKTILKKAGIG CV VSSIFFINKQ P (TAFlB(-l) ) ;
  • EIFLPKGRSNSKKKGRRNRIPAVLRTEGEPLHTPSVGMRETTGLGC (HT001 (-1) ) ; HSTIKVIKAKKKHREVKRTNSSQLV (AIM2 (-1) ) ;
  • the term "functional equivalent” as used herein relates to, e.g., variants or fragments of the FSP which are still capable of eliciting an immune response against the cancer, i.e., are still useful as an efficient vaccine.
  • An immune response is defined as a condition fulfilling at least one of the following criteria: 1. The induction of CD8-positive T cells, as detectable by cytotoxicity assays or IFN-gamma secretion or perforin expression or granzyme B expression or other cytokines that may be produced by CD8-positive T cells, measurable as above background by ELISpot or intracellular cytokine staining or cytokine ELISA or equivalent methods. 2.
  • Cytokines may comprise IFN-alpha, IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, TNF-alpha, TGF-beta or other cytokines that may be produced by CD4-positive T cells.
  • the induction of antibodies as detectable by Western blot, ELISA and equivalent or related methods. 4.
  • the variants are characterized by amino acid deletions, substitutions, and/or additions. Preferably, amino acid differences are due to one or more conservative amino acid substitutions.
  • conservative amino acid substitutions involves replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and lie; replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues Asp and Glu; replacement of the amide residues Asn and Gin, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly.
  • peptides showing a particular degree of identity to the FSP e.g., genetic engineering can be used to introduce amino acid changes at specific positions of a cloned DNA sequence to identify regions critical for peptide function.
  • genetic engineering can be used to introduce amino acid changes at specific positions of a cloned DNA sequence to identify regions critical for peptide function.
  • site directed mutagenesis or alanine-scanning mutagenesis introduction of single alanine mutations at every residue in the molecule
  • the resulting mutant molecules can then be tested for immunogenicity using the assay of Example 1.
  • the variants are characterized by not more than 8 aa, more preferably by not more than 6 aa and, even more preferably, by not more than 4 aa substitutions, deletions and/or additions.
  • At least 5 contiguous aa preferably at least 10 contiguous aa, more preferably at least contiguous 15 aa and even more preferably at least 20 contiguous aa of the particular amino acid sequence are left.
  • the fragment is still capable of eliciting an immune response .
  • the vaccine of the present invention additionally comprises an adjuvant and/or immunostimulatory cytokine or chemokine.
  • Suitable adjuvants include an aluminium salt such as aluminium hydroxide gel (alum) or aluminium phosphate, but may also be a salt of calcium, iron or zinc, or may be an insoluble suspension of acylated tyrosine, or acylated sugars, cationically or anionicaily derivatised polysaccharides, or polyphosphazenes .
  • Other known adjuvants include CpG containing oligonucleotides. The oligonucleotides are characterised in that the CpG dinucleotide is unmethylated . Such oligonucleotides are well known and are described in, for example WO 96/02555.
  • immunostimulatory cytokines have become an increasingly promising approach in cancer immunotherapy.
  • the major goal is the activation of tumour-specific T lymphocytes capable of rejecting tumour cells from patients with low tumour burden or to protect patients from a recurrence of the disease.
  • Strategies that provide high levels of immunostimulatory cytokines locally at the site of antigen have demonstrated pre-clinical and clinical efficacy.
  • Preferred immunostimulatory cytokines comprise IL-2, IL-4, IL-7, IL-12, IFNs, GM-CSF and TNF-oi .
  • Chemokines are small (7-16 kD) , secreted, and structurally related soluble proteins that are involved in leukocyte and dendritic cell chemotaxis, PMN degranulation, and angiogenesis . Chemokines are produced during the initial phase of host response to injury, allergens, antigens, or invading microorganisms. Chemokines selectively attract leukocytes to inflammatory foci, inducing both cell migration and activation. Chemokines may enhance innate or specific host immunity against tumors and, thus may also be useful in combination with an FSP.
  • the vaccine of the present invention might also contain a nucleic acid encoding the FSP for DNA immunization, a technique used to efficiently stimulate humoral and cellular immune responses to protein antigens.
  • the direct injection of genetic material into a living host causes a small amount of its cells to produce the introduced gene products. This inappropriate gene expression within the host has important immunological consequences, resulting in the specific immune activation of the host against the gene delivered antigen.
  • Direct injection of naked plasmid DNA induces strong immune responses to the antigen encoded by the gene vaccine. Once the plasmid DNA construct is injected the host cells take up the foreign DNA, expressing the viral gene and producing the FSP inside the cell.
  • the DNA vaccines are composed of vectors normally containing two unites: the antigen expression unit composed of promoter/enhancer sequences, followed by antigen ( FSP) -encoding and polyadenylation sequences and the production unit composed of sequences necessary for vector amplification and selection.
  • the construction of vectors with vaccine inserts is accomplished using recombinant DNA technology and the person skilled in the art knows vectors that can be used for this approach.
  • the efficiency of DNA immunization can be improved by stabilising DNA against degradation, and increasing the efficiency of delivery of DNA into antigen presenting cells.
  • biodegradable cationic microparticles such as poly ( lactide-co-glycolide) formulated with cetyltrimethylammonium bromide
  • DNA-coated microparticles can be as effective at raising CTL as recombinant vaccinia viruses, especially when mixed with alum.
  • Particles 300 nm in diameter appear to be most efficient for uptake by antigen presenting cells.
  • a variety of expression vectors e.g., plasmids or viral vectors, may be utilised to contain and express nucleic acid sequences encoding an FSP of the present invention.
  • a preferred viral vector is a poxvirus, adenovirus, retrovirus, herpesvirus or adeno-associated virus (AAV) .
  • poxviruses are a vaccinia virus, YVAC, avipox virus, canarypox virus, ALVAC, ALVAC(2), fowlpox virus or TROVAC.
  • alphavirus-based vectors have also been used to improve DNA vaccination efficiency.
  • the gene encoding the FSP is inserted into the alphavirus replicon, replacing structural genes but leaving non-structural replicase genes intact.
  • the Sindbis virus and Semliki Forest virus have been used to build recombinant alphavirus replicons. Unlike conventional DNA vaccinations, however, alphavirus vectors are only transiently expressed. Alphavirus replicons raise 12 005154
  • the FSP contains a Tag sequence, preferably at the C-terminus which might be useful for purification of a recombinantly produced FSP.
  • a preferred Tag sequence is a His-Tag.
  • a particularly preferred His-Tag consists of 6 His-residues.
  • the vaccine of the present invention is administered in an amount suitable for immunization of an individual and, preferably, additionally contains one or more common auxiliary agents.
  • amount suitable for immunization of an individual comprises any amount of FSP with which an individual can be immunized. The amount depends on whether immunization is intended as a prophylactic or therapeutic treatment. In addition, the individual's age, sex and weight play a role for determining the amount. Thus, the amount suitable for immunization of an individual refers to amounts of the active ingredients that are sufficient to affect the course and the severity of the tumor, leading to the reduction or remission of such pathology.
  • an “”amount suitable for immunization of an individual” may be determined using methods known to one skilled in the art (see for example, Fingl et al., 1975).
  • the term "individual” as used herein comprises an individual of any kind and being able to fall ill with carcinomas. Examples of such individuals are humans and animals as well as cells thereof.
  • the administration of the vaccine by injection may be made at various sites of the individual intramuscularly, subcutaneously, intradermally or in any other form of application. It may also be favourable to carry out one or more "booster injections" having about equal amounts.
  • auxiliary agents comprises any auxiliary agents suitable for a vaccine to immunize an individual.
  • auxiliary agents are, e.g., buffered common salt solutions, water, emulsions, such as oil/water emulsions, wetting agents, sterile solutions, etc.
  • An FSP, nucleic acid sequence or vector of the present invention can be present in the vaccine as such or in combination with carriers. It is favourable for the carriers in the individual not to be immunogenic. Such carriers may be the individual's own proteins or foreign proteins or fragments thereof. Carriers, such as serum albumin, fibrinogen or transferrin or a fragment thereof are preferred.
  • the vaccine of the present invention may be therapeutic, that is, the compounds are administered to treat an existing cancer, or to prevent the recurrence of a cancer, or prophylactic, that is, the compounds are administered to prevent or delay the development of cancer. If the compositions are used therapeutically, they are administered to cancer patients and are designed to elicit an immune response to stabilize a tumor by preventing or slowing the growth of the existing cancer, to prevent the spread of a tumor or of metastases, to reduce the tumor size, to prevent the recurrence of treated cancer, or to EP2012/005154
  • a vaccine used as a prophylactic treatment is administered to individuals who do not have cancer, and are designed to elicit an immune response to target potential cancer cells.
  • the present invention also relates to the use of an FSP or functional equivalent, nucleic acid sequence or vector as defined above for the production of a vaccine for the prevention of a carcinoma, e.g., preventive vaccination of a high risk group, or treatment of a carcinoma.
  • a carcinoma e.g., preventive vaccination of a high risk group, or treatment of a carcinoma.
  • these may be a colorectal cancer, preferably a hereditary non-polyposis colorectal cacner (HNPCC) , an endometrial cancer, a gastric cancer or small bowel cancer.
  • HNPCC hereditary non-polyposis colorectal cacner
  • PTc day 0, lxl0 5 /well
  • autologous CD40-activated B cells 4xl0 4 /well, TiBc or pBc, respectively
  • Peptides were added at a final concentration of 10 ⁇ g/mL.
  • pTc were treated with 20 nmol/L phorbol-12-myristate-13- acetate in combination 350 nmol/L ionomycin.
  • I specific antigens (CD19 and CD23) were used as antigen- presenting cells.
  • TGFBR2 (-1) ASPKCIMKEKKSLVRLSSCVPVALMSAMTTSSSQKNITPAILTCC
  • peptides were coated to 96 well polystyrol microtiter plates "Maxisorp"' (Nunc, Roskilde, Denmark) at a concentration of 40 ug/ml in PBS overnight at 4 °C. After coating, plates were washed 4 times with PBS (0.05% Tween) and blocked for 1 h with 0.5% casein in PBS. Peptide binding to the microtiter plates and optimal saturating peptide concentration were assessed using an alkaline phosphatase- peptide competition assay.
  • a control peptide derived from the pl6 INK4a protein (pl6_76-105) was used, against which no antibody reactivity was found in a large cohort of individuals (Reuschenbach et al . , 2008).
  • Each serum was diluted 1:100 in blocking buffer (0.5% casein in PBS) and tested in duplicates for the presence of antibodies against all FSPs and the control peptide.
  • blocking buffer (0.5% casein in PBS
  • one control serum was included on every plate, and peptide specific ODs of the control serum were used for normalization.
  • CD107a surface expression on T effector cells upon stimulation with the clinical FSP antigens was measured.
  • CD107a assays are used to demonstrate secretion of cytotoxic granula containing perforin/granzyme B from effector cells.
  • CD107a molecules are expressed on the surface of cytotoxic granula and become detectable on the cell surface if granula are released in the context of a cytotoxic T cell response.
  • T cells were stimulated with the FSPs using dendritic cells as antigen-presenting cells. Stimulation was repeated weekly and over a time span of four weeks. After four weeks, T cells were harvested and coincubated with target cells and FSPs CD107a assay was used to analyze peptide-specific induction of a cytotoxic T cell response.
PCT/EP2012/005154 2012-12-13 2012-12-13 Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer WO2014090265A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
BR112015013737-7A BR112015013737B1 (pt) 2012-12-13 2012-12-13 Peptídeos com alteração do quadro de leitura msiespecífico (fsp) para a prevenção e tratamento do câncer
RU2015115785A RU2644677C2 (ru) 2012-12-13 2012-12-13 Мсн-специфичные пептиды со смещенной рамкой считывания (псрс) для предотвращения и лечения рака
KR1020157015802A KR101810840B1 (ko) 2012-12-13 2012-12-13 암의 예방 및 치료용 msi-특이적 프레임쉬프트 펩티드(fsp)
PCT/EP2012/005154 WO2014090265A1 (en) 2012-12-13 2012-12-13 Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer
CN201280077683.XA CN104853764B (zh) 2012-12-13 2012-12-13 用于预防和治疗癌症的msi-特异性移码肽(fsp)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2012/005154 WO2014090265A1 (en) 2012-12-13 2012-12-13 Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer

Publications (1)

Publication Number Publication Date
WO2014090265A1 true WO2014090265A1 (en) 2014-06-19

Family

ID=47552936

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2012/005154 WO2014090265A1 (en) 2012-12-13 2012-12-13 Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer

Country Status (5)

Country Link
KR (1) KR101810840B1 (ru)
CN (1) CN104853764B (ru)
BR (1) BR112015013737B1 (ru)
RU (1) RU2644677C2 (ru)
WO (1) WO2014090265A1 (ru)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021239980A2 (en) 2020-05-28 2021-12-02 Hubro Therapeutics As A peptide cocktail
EP4052716A1 (en) 2021-03-04 2022-09-07 Deutsches Krebsforschungszentrum - Stiftung des öffentlichen Rechts / Universität Heidelberg Cancer therapy involving car-engineered t-cells and parvovirus h-1

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018223093A1 (en) * 2017-06-02 2018-12-06 Arizona Board Of Regents On Behalf Of Arizona State University Universal cancer vaccines and methods of making and using same
CN111328420B (zh) * 2017-07-12 2023-07-25 Nouscom股份公司 用于预防和治疗微卫星不稳定(msi)癌症的基于共有肿瘤新抗原的通用疫苗

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996002555A1 (en) 1994-07-15 1996-02-01 The University Of Iowa Research Foundation Immunomodulatory oligonucleotides
WO2003087162A2 (en) * 2002-04-18 2003-10-23 Mtm Laboratories Ag Neopeptides and methods useful for detection and treatment of cancer
EP2572725A1 (en) * 2011-09-21 2013-03-27 Ruprecht-Karls-Universität Heidelberg MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101385805B1 (ko) * 2005-11-30 2014-04-16 인터내셔널 인스티튜트 오브 캔서 이무놀로지 인코퍼레이티드 신규 펩티드 화합물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996002555A1 (en) 1994-07-15 1996-02-01 The University Of Iowa Research Foundation Immunomodulatory oligonucleotides
WO2003087162A2 (en) * 2002-04-18 2003-10-23 Mtm Laboratories Ag Neopeptides and methods useful for detection and treatment of cancer
EP2572725A1 (en) * 2011-09-21 2013-03-27 Ruprecht-Karls-Universität Heidelberg MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
CUNNINGHAM; WELLS, SCIENCE, vol. 244, 1989, pages 1081 - 1085
FINGL ET AL.: "The Pharmocological Basis of Therapeutics", 1975, MACMILLAN PUBLISHING CO., pages: 1 - 46
KATHRIN BAUER ET AL: "Dendritic cell and macrophage infiltration in microsatellite-unstable and microsatellite-stable colorectal cancer", FAMILIAL CANCER, KLUWER ACADEMIC PUBLISHERS, DO, vol. 10, no. 3, 20 May 2011 (2011-05-20), pages 557 - 565, XP019954561, ISSN: 1573-7292, DOI: 10.1007/S10689-011-9449-7 *
KATHRIN BAUER ET AL: "T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer", CANCER IMMUNOLOGY, IMMUNOTHERAPY, SPRINGER, BERLIN, DE, vol. 62, no. 1, 23 June 2012 (2012-06-23), pages 27 - 37, XP035162540, ISSN: 1432-0851, DOI: 10.1007/S00262-012-1303-8 *
KLOOR M; MICHEL S; VON KNEBEL DOEBERITZ M: "Immune evasion of microsatellite unstable colorectal cancers", INT J CANCER, 2 March 2010 (2010-03-02)
KLOOR MATTHIAS ET AL: "Immune evasion of microsatellite unstable colorectal cancers.", INTERNATIONAL JOURNAL OF CANCER. JOURNAL INTERNATIONAL DU CANCER 1 SEP 2010 LNKD- PUBMED:20198617, vol. 127, no. 5, 1 September 2010 (2010-09-01), pages 1001 - 1010, XP002676135, ISSN: 1097-0215 *
LINNEBACHER M ET AL: "Frameshift peptide-derived T-cell epitopes: a source of novel tumor-specific antigens", INTERNATIONAL JOURNAL OF CANCER, JOHN WILEY & SONS, INC, UNITED STATES, SWITZERLAND, GERMANY, vol. 93, no. 1, 1 July 2001 (2001-07-01), pages 6 - 11, XP001061478, ISSN: 0020-7136, DOI: 10.1002/IJC.1298 *
LINNEBACHER M; GEBERT J; RUDY W; WOERNER S; YUAN YP; BORK P; VON KNEBEL DOEBERITZ M.: "Frameshift peptide-derived T-cell epitopes: a source of novel tumor-specific antigens", INT J CANCER., vol. 93, no. 1, 1 July 2001 (2001-07-01), pages 6 - 11
MIRIAM REUSCHENBACH ET AL: "Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome", FAMILIAL CANCER, KLUWER ACADEMIC PUBLISHERS, DO, vol. 9, no. 2, 2 December 2009 (2009-12-02), pages 173 - 179, XP019818173, ISSN: 1573-7292 *
REUSCHENBACH M; KLOOR M; MORAK M; WENTZENSEN N; GERMANN A; GARBE Y; TARIVERDIAN M; FINDEISEN P; NEUMAIER M; HOLINSKI-FEDER E: "Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome", FAM CANCER, 2 December 2009 (2009-12-02)
REUSCHENBACH M; WATERBOER T; WALLIN KL; EINENKEL J; DILLNER J; HAMSIKOVA E; ESCHENBACH D; ZIMMER H; HEILIG B; KOPITZ J: "Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV-associated cancers", INT J CANCER, vol. 123, no. 11, 1 December 2008 (2008-12-01), pages 2626 - 31, XP055020730, DOI: doi:10.1002/ijc.23837
RIPBERGER E; LINNEBACHER M; SCHWITALLE Y; GEBERT J; VON KNEBEL DOEBERITZ M.: "Identification of an HLA-A0201- restricted CTL epitope generated by a tumor-specific frameshift mutation in a coding microsatellite of the OGT gene", J CLIN IMMUNOL., vol. 23, no. 5, September 2003 (2003-09-01), pages 415 - 23, XP002676134, DOI: doi:10.1023/A:1025329819121
RIPBERGER EVA ET AL: "Identification of an HLA-A0201-restricted CTL epitope generated by a tumor-specific frameshift mutation in a coding microsatellite of the OGT gene.", JOURNAL OF CLINICAL IMMUNOLOGY SEP 2003 LNKD- PUBMED:14601650, vol. 23, no. 5, September 2003 (2003-09-01), pages 415 - 423, XP002676134, ISSN: 0271-9142 *
SCHWITALLE Y ET AL: "Immune Response Against Frameshift-Induced Neopeptides in HNPCC Patients and Healthy HNPCC Mutation Carriers", GASTROENTEROLOGY, ELSEVIER, PHILADELPHIA, PA, vol. 134, no. 4, 1 April 2008 (2008-04-01), pages 988 - 997, XP022584833, ISSN: 0016-5085, [retrieved on 20080111], DOI: 10.1053/J.GASTRO.2008.01.015 *
SCHWITALLE Y; KLOOR M; EIERMANN S; LINNEBACHER M; KIENLE P; KNAEBEL HP; TARIVERDIAN M; BENNER A; VON KNEBEL DOEBERITZ M.: "Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers", GASTROENTEROLOGY, vol. 134, no. 4, April 2008 (2008-04-01), pages 988 - 97, XP022584833, DOI: doi:10.1053/j.gastro.2008.01.015
SCHWITALLE Y; LINNEBACHER M; RIPBERGER E; GEBERT J; VON KNEBEL DOEBERITZ M.: "Immunogenic peptides generated by frameshift mutations in DNA mismatch repair-deficient cancer cells", CANCER IMMUN, vol. 4, 25 November 2004 (2004-11-25), pages 14, XP009159420
SCHWITALLE YVETTE ET AL: "Immunogenic peptides generated by frameshift mutations in DNA mismatch repair-deficient cancer cells.", CANCER IMMUNITY 25 NOV 2004 LNKD- PUBMED:15563124, vol. 4, 25 November 2004 (2004-11-25), pages 14, XP009159420, ISSN: 1424-9634 *
TOUGERON DAVID ET AL: "Tumor-infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frameshift mutations.", MODERN PATHOLOGY : AN OFFICIAL JOURNAL OF THE UNITED STATES AND CANADIAN ACADEMY OF PATHOLOGY, INC SEP 2009 LNKD- PUBMED:19503063, vol. 22, no. 9, September 2009 (2009-09-01), pages 1186 - 1195, XP002676136, ISSN: 1530-0285 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021239980A2 (en) 2020-05-28 2021-12-02 Hubro Therapeutics As A peptide cocktail
WO2021239980A3 (en) * 2020-05-28 2022-02-24 Hubro Therapeutics As A peptide cocktail
EP4052716A1 (en) 2021-03-04 2022-09-07 Deutsches Krebsforschungszentrum - Stiftung des öffentlichen Rechts / Universität Heidelberg Cancer therapy involving car-engineered t-cells and parvovirus h-1
WO2022184824A2 (en) 2021-03-04 2022-09-09 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Cancer therapy involving car-engineered t-cells and parvovirus h-1

Also Published As

Publication number Publication date
BR112015013737B1 (pt) 2021-07-27
RU2644677C2 (ru) 2018-02-13
CN104853764A (zh) 2015-08-19
BR112015013737A2 (pt) 2017-07-11
KR20150084060A (ko) 2015-07-21
KR101810840B1 (ko) 2017-12-20
CN104853764B (zh) 2018-06-22
RU2015115785A (ru) 2017-01-16

Similar Documents

Publication Publication Date Title
US10682402B2 (en) MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer
JP5689140B2 (ja) 胃癌およびその他のがんの治療に用いる腫瘍関連ペプチド組成物と関連抗がんワクチン
WO2015106697A1 (zh) 免疫增强的人乳头瘤病毒感染及相关疾病的治疗性疫苗
US20220233666A1 (en) Cancer vaccine
EP2572725B1 (en) MSI-specific frameshift peptides (FSP) for prevention and treatment of cancer
WO2014090265A1 (en) Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer
JP5890769B2 (ja) がんの予防及び治療のためのｍｓｉ特異的なフレームシフトペプチド（ｆｓｐ）
JP2016028025A (ja) がんの予防及び治療のためのｍｓｉ特異的なフレームシフトペプチド（ｆｓｐ）
CN112088012A (zh) 诱导免疫应答的组合物和方法
AU2016201986B2 (en) MSI-specific Frameshift Peptides (FSP) for Prevention and Treatment of Cancer
CA2799803C (en) Msi-specific frameshift peptides (fsp) for prevention and treatment of cancer
EP2573105B1 (en) p16INK4a derived peptides for prophylaxis and therapy of HPV-associated tumors and other p16INK4a expressing tumors
US9566319B2 (en) p16INK4a derived peptides for prophylaxis and therapy of HPV-associated tumors and other p16INK4a expressing tumors
CA2799804C (en) P16ink4a derived peptides for prophylaxis and therapy of hpv-associated tumors and other p16ink4a expressing tumors
JP6238477B2 (ja) ＨＰＶ関連腫瘍及び他のｐ１６ＩＮＫ４ａ発現腫瘍の予防法及び治療法のためのｐ１６ＩＮＫ４ａ由来ペプチド
AU2012261781B2 (en) p16INK4a Derived Peptides for Prophylaxis and Therapy of HPV-associated Tumors and other p16INK4a Expressing Tumors
JP5946759B2 (ja) ＨＰＶ関連腫瘍及び他のｐ１６ＩＮＫ４ａ発現腫瘍の予防法及び治療法のためのｐ１６ＩＮＫ４ａ由来ペプチド
WO2002068653A2 (en) Tri-hybrid melanoma antigen
Class et al. Patent application title: COMPOSITION OF TUMOR-ASSOCIATED PEPTIDES AND RELATED ANTI-CANCER VACCINE FOR THE TREATMENT OF GASTRIC CANCER AND OTHER CANCERS Inventors: Jens Fritsche (Tuebingen, DE) Jens Fritsche (Tuebingen, DE) Toni Weinschenk (Aichwald, DE) Steffen Walter (Reutlingen, DE) Steffen Walter (Reutlingen, DE) Peter Lewandrowski (Tuebingen-Hirschau, DE) Peter Lewandrowski (Tuebingen-Hirschau, DE) Harpeet Singh (Tuebingen, DE) Assignees: IMMATICS BIOTECHNOLOGIES GMBH
AU2002244196A1 (en) Tri-hybrid melanoma antigen

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12813270

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 20157015802

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112015013737

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 2015115785

Country of ref document: RU

Kind code of ref document: A

122 Ep: pct application non-entry in european phase

Ref document number: 12813270

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 112015013737

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20150611