PHARMACEUTICAL COMPOSITION, PHARMACEUTICAL KIT, IMMUNOTHERAPEUTIC COMPOSITION OR VACCINE AND ITS USE IN THE TREATMENT OR PREVENTION OF CANCER.

Abstract

The description relates to polypeptides and pharmaceutical compositions comprising polypeptides that are useful in the prevention or treatment of cancer, particularly breast cancer, ovarian cancer, and colorectal cancer. The description also relates to methods for inducing a cytotoxic T-cell response in a subject or treating cancer by administering pharmaceutical compositions comprising the peptides, and to accompanying diagnostic methods for identifying subjects for treatment. The peptides comprise T-cell epitopes that are immunogenic in a high percentage of patients.

Description

VACCINE COUNTRYSIDE The disclosure relates to polypeptides and vaccines that may be useful in the prevention or treatment of cancer, in particular most breast, ovarian, and colorectal cancers. BACKGROUND Cancer is killing millions of people around the world, because existing drugs do not allow effective prevention or treatment. Current checkpoint inhibitor immunotherapies that reactivate existing immune responses may provide clinical benefit for a fraction of cancer patients. Current cancer vaccines that induce new immune responses are poorly immunogenic and cannot benefit most patients. Recent analyzes of 63,220 unique tumors revealed that cancer vaccines need to be generated specifically for each patient due to extensive tumor genomic heterogeneity between individuals (Hartmaier et al. Genome Medicine 2017 9:16). Using state-of-the-art technologies, it is currently not feasible to tailor HLA-specific cancer vaccines to larger populations. COMPENDIUM In antigen presenting cells (APC), protein antigens are processed to form peptides. These peptides bind to human leukocyte antigen (HLA) molecules and are presented on the cell surface as peptide-HLA complexes to T cells. Different individuals express different HLA molecules, and different HLA molecules present different peptides. Thus, according to the state of the art, a peptide, or a fragment of a larger polypeptide, is identified as being immunogenic for a specific human subject if it is presented by an HLA molecule that is expressed by the subject. In other words, the state of the art describes immunogenic peptides as HLA-restricted epitopes. However, HLA-restricted epitopes induce T cell responses in only a fraction of individuals expressing the HLA molecule. Peptides that activate a T cell response in one individual are inactive in others despite matching HLA alleles. Therefore, it was previously unknown how an individual's HLA molecules present the antigen-derived epitopes that positively activate T cell responses. As provided herein, multiple HLAs expressed by an individual must present the same peptide to activate a T cell response. Fragments of a polypeptide antigen that are immunogenic for a specific individual are those that can bind multiple HLAs. class I (activate cytotoxic T lymphocytes) or class II (activate helper T lymphocytes) expressed by that individual. For example, the inventors discovered that the presence of a T-cell epitope that binds to at least three type I HLAs from a subject predicts an immune response in the subject to a polypeptide. Based on this discovery, the inventors identified the T cell epitopes of certain polypeptide antigens associated with breast, ovarian, and / or colorectal cancer (testicular cancer antigens (CTAs)) that are capable of binding to at least three HLAs of class I in a high proportion of individuals. These T cell epitopes, or fragments of the antigens comprising the T cell epitopes, are useful for inducing specific immune responses against tumor cells expressing these antigens and for treating or preventing cancer. In a first aspect, the description provides a polypeptide comprising a fragment of up to 50 consecutive amino acids of (a) a colorectal cancer-associated antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, LEMD1, MAGE-A8, MAGE -A6 and MAGE-A3, wherein the fragment comprises an amino acid sequence selected from any of SEQ TD NO: 21 to 40 and 234 to 250; (b) an ovarian cancer-associated antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN, and AKAP-3, wherein the fragment comprises the amino acid sequence of any of SEQ ID NO: from 272 to 301; and / or (c) a breast cancer associated antigen selected from PIWIL-2, AKAP-4, EpCAM, BORIS, HIWI, SPAG9, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, PRAME, NY -SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-A11, HOM-TES-85 and NY-ESO-1, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: from 1 to 20, 24 and from 172 to 194. In some specific instances, the disclosure provides a polypeptide that (a) is a fragment of a colorectal cancer-associated antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3 and LEMD1, where the fragment comprises an amino acid sequence selected from any of SEQ ID NO: from 21 to 40 and from 234 to 250 ; or (b) comprises or consists of two or more fragments of one or more colorectal cancer-associated antigens selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3 and LEMD1, in wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 21 to 40 and 234 to 250, wherein the fragments optionally overlap or are arranged end-to-end in the polypeptide; or(c) is a fragment of an ovarian cancer-associated antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME , HIWI, SURVIVIN and AKAP-3, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 272 to 301; or(d) comprises or consists of two or more fragments of one or more ovarian cancer-associated antigens selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 272 to 301, wherein the fragments optionally overlap or are arranged end-to-end in the polypeptide; o(e) is a fragment of a breast cancer-associated antigen selected from SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM -TES-85, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, where the fragment comprises the amino acid sequence of any of SEQ ID NO: from 1 to 20, 24 and from 172 to 194; or(f) comprises or consists of two or more fragments of one or more breast cancer associated antigens selected from SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM-TES-8, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: from 1 to 20, 24 and from 172 to 194; wherein, optionally, the fragments overlap or are arranged end-to-end in the polypeptide. In some specific cases, the polypeptide comprises or consists of fragments of (a) TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3 and LEMDl; (b) PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN, and AKAP-3; and / or (c) SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM-TES-8, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2; where each fragment comprises a different amino acid sequence selected from SEQ ID NO: from 21 to 40 and from 234 to 250; SEQ ID NO: from 272 to 301; and / or SEQ ID NO: from 1 to 20, 24 and from 172 to 194. In some cases, the polypeptide comprises or consists of one or more amino acid sequences selected from SEQ ID NO: 41-80, from 251 to 271, from 302 to 331 and from 196 to 233. In some cases, the polypeptide comprises or consists of one or more amino acid sequences selected from SEQ ID NO: 41-80, 195-233, 251-271 and 302-331 or selected from SEQ ID NO: 81-142, 332- 346 and 435-449. In a further aspect, the disclosure provides a panel of two or more polypeptides as described above, wherein each peptide comprises or consists of a different amino acid sequence selected from SEQ ID NO: 21 to 40 and 234 to 250; selected from SEQ ID NO: 272 to 301; selected from SEQ ID NO: 1 to 20, 24 and 172 to 194; or selected from SEQ ID NO: 1 to 40, 234 to 250, 272 to 301 and 172 to 194. In some cases, the polypeptide panel comprises or consists of one or more peptides comprising or consisting of the sequences of amino acids of SEQ ID NO: 130, 121, 131, 124, 134, 126 and / or SEQ ID NO: 435-449. In a further aspect, the description provides a pharmaceutical composition or kit having one or more polypeptides or panels of peptides as described above as active ingredients, or having a polypeptide comprising at least two amino acid sequences selected from SEQ ID NO: from 21 to 40 and from 234 to 250; SEQ ID NO: from 272 to 301; and / or SEQ ID NO: from 1 to 20, 24 and from 172 to 194 as an active ingredient; or selected from SEQ ID NO: 130, 121, 131, 124, 134, 126 and / or 435-449 as an active ingredient. In a further aspect, the disclosure provides a method of inducing immune responses (eg, vaccination, provision of immunotherapy, or induction of a cytotoxic T-lymphocyte response in a subject), wherein the method comprises administering to the subject a pharmaceutical composition, a kit or panel of polypeptides as described above. The method may be a method of treating cancer, such as breast cancer, ovarian cancer, or colorectal cancer. In other aspects, the disclosure provides the pharmaceutical composition, kit, or panel of polypeptides described above for use in a method of inducing immune responses or for use in a method of treating cancer, optionally breast cancer, ovarian cancer, or colorectal cancer. ; and the use of a peptide or panel of peptides as described above in the manufacture of a medicament for inducing immune responses or for treating cancer, optionally breast cancer, ovarian cancer or colorectal cancer. In a further aspect, the composition provides a method of identifying a human subject likely to have a cytotoxic T-lymphocyte response to administration of a pharmaceutical composition as described above, wherein the method comprises (i) determining that the polypeptides of the active ingredient of the pharmaceutical composition comprise a sequence that is an epitope of T lymphocytes capable of binding to at least three HLA class I of the subject; and (ii) identifying that the subject is likely to have a cytotoxic T-lymphocyte response to administration of the pharmaceutical composition. In a further aspect, the disclosure provides a method of identifying a subject likely to have a clinical response to a method of treatment as described above, wherein the method comprises (i) determining that the active ingredient polypeptides comprise two or more sequences of different amino acids, each of which is a. a T cell epitope capable of binding to at least three HLA class I of the subject; and b. a fragment of a cancer-associated antigen expressed by cancer cells of the subject; and (ii) identify that the subject is likely to have a clinical response to the method of treatment. In a further aspect, the description provides a method for determining the probability that a specific human subject will have a clinical response to a method of treatment according to claim 10, wherein one or more of the following factors correspond to a higher probability of a clinical response: (a) presence in the polypeptides of the active ingredient of a greater number of amino acid sequences and / or different amino acid sequences that are, each, an epitope of T lymphocytes capable of binding to at least three HLA of class I of the subject; (b) a greater amount of target polypeptide antigens comprising at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B. is a T cell epitope capable of binding to at least three HLA class I of the subject; wherein, optionally, the target polypeptide antigens are expressed in the subject, further optionally wherein the target polypeptide antigens are found in one or more samples obtained from the subject; (c) an increased probability that the subject will express target polypeptide antigens, optionally a threshold amount of the target polypeptide antigens, and / or optionally target polypeptide antigens determined to comprise at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B. is a T cell epitope capable of binding to at least three HLA class I of the subject; and / or (d) a greater number of target polypeptide antigens than the subject is predicted to express, optionally a greater number of target polypeptide antigens than the subject expresses with a threshold probability, and / or optionally the target polypeptide antigens that the subject expresses. have been determined to comprise at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B. it is a T cell epitope capable of binding to at least three HLA class I of the subject. In some cases, cancer-associated antigens may be TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, LEMD1, MAGE-A8, MAGE-A6, MAGE-A3, PIWIL-4, WT1, BORIS, AKAP-4, OY -TES-1, SP17, PIWIL-2, PIWIL-3, PRAME, HIWI, PLU-1, TSGA10, ODF-4, RHOXF-2, NY-SAR-35, MAGE-A9, NY-BR-1, MAGE -A11, HOM-TES-85, NY-ESO-1 and AKAP-3. In some cases, the above methods comprise the step of determining that one or more cancer-associated antigens are expressed by cancer cells of the subject. Cancer-associated antigens may be present in one or more samples obtained from the subject. In some cases, administration of the pharmaceutical composition or the active ingredient polypeptides of the kit may then be selected as a method of treatment for the subject. The subject may further be treated by administration of the pharmaceutical composition or the active ingredient polypeptides. In a further aspect, the disclosure provides a method of treatment as described above, wherein the subject has been identified as likely to have a clinical response or as having a minimal probability above a threshold of having a clinical response to treatment at through the method described above. In a further aspect, the description provides a method of identifying a human subject that is not likely to have a clinical response to a method of treatment as described above, wherein the method comprises (i) determining that the polypeptides of the active ingredient of the composition pharmaceutical do not comprise two or more different amino acid sequences, each of which is a T cell epitope capable of binding to at least three HLA class I of the subject; and (ii) identify that the subject is not likely to have a clinical response to the method of treatment. The methods described above may comprise the step of determining the HLA class I genotype of the subject. The description will now be described in more detail, by way of example and not limitation, and by reference to the accompanying drawings. Many equivalent modifications and variations will be apparent to those skilled in the art when provided with the present description. Accordingly, the exemplary embodiments of the stated description are considered illustrative and not exhaustive. Various changes may be made to the described embodiments without departing from the scope of the description. All documents cited herein, either above or below, are expressly incorporated by reference in their entirety. The present description includes the combination of the aspects and preferred features described, except in the case that said combination clearly cannot be admitted or it is established that it is expressly avoided. As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a peptide" includes two or more such peptides. The section headings are used herein for convenience only and should not be construed as limiting in any way. DESCRIPTION OF THE FIGURES Figure 1 ROC curve of HLA-restricted PEPI biomarkers. Figure 2 ROC curve test of <1 PEPI3+ for determination of diagnostic accuracy. Figure 3A PEPI3+ distribution of HLA class I compared to CD8+ T-cell responses measured by a state-of-the-art assay among peptide pools used in CD8+ T-cell response assays. PEPI3+ restricted by HLA class I. The overall percentage of agreement (OPA) of 90% between T-cell responses and PEPI3+ peptides demonstrates the utility of the invented peptides for predicting the ensemble of T-cell responses induced by PEPI3+. vaccination of individuals. Figure 3B PEPI3+ distribution of HLA class I compared to CD8+ T-cell responses measured by a state-of-the-art assay among peptide pools used in CD8+ T-cell response assays. HLA class I restricted epitopes (PEPI1+). The OPA between predicted epitopes and CD8+ T cell responses was 28% (not statistically significant). Darkest gray: true positive (TP), peptide responses detected; and of T lymphocytes; Light gray: false negative (FN), only T cell responses detected; Lightest gray: false positive (FP), only peptide detected; Dark gray: true negative (TN): neither peptides nor T cell responses were detected. Figure 4A HLA class II PEPI distribution compared to CD4+ T cell responses measured by a state-of-the-art assay among the peptide pools used in the assays. PEPI4+ restricted by HLA class II. 67% OPA between PEPI4+ and CD4+ T cell responses (p=0.002). Figure 4B HLA class II PEPI distribution compared to CD4+ T cell responses measured by a state-of-the-art assay among the peptide pools used in the assays. HLA class II restricted epitopes. The OPA between HLA class II restricted epitopes and CD4+ T cell responses was 66% (not statistically significant). Darkest gray: true positive (TP), peptide responses detected; and of T lymphocytes; Light gray: false negative (FN), only T cell responses detected; Lightest gray: false positive (FP), only peptide detected; Dark gray: true negative (TN): neither peptides nor T cell responses were detected. Figure 5A and 5B Multiple HLA-binding peptides defining the set of HPV-16 LPV vaccine-specific T cell responses from 18 VIN-3 and 5 cervical cancer patients. PEPI3 counts restricted by HLA class I; Dark gray: immune non-responders measured after vaccination in the clinical trial. The results show that Ü 3 HLA class I binding peptides predict CD8+ T cell reactivity and = 4 HLA class II binding peptides predict CD4+ T cell reactivity. Figure 5C and 5D Multiple HLA-binding peptides defining the set of HPV-16 LPV vaccine-specific T cell responses from 18 VIN-3 and 5 cervical cancer patients. HLA class II restricted PEPI3 counts derived from LPV antigens from each patient. Light gray: immune responders measured after vaccination in the clinical trial; Dark gray: immune non-responders measured after vaccination in the clinical trial. The results show that = 3 HLA class I binding peptides predict CD8+ T cell reactivity and = 4 HLA class II binding peptides predict CD4+ T cell reactivity. Figure 6A The multiple HLA class I-binding peptides that define the HPV vaccine-specific set of T cell responses from 2 patients. Four HPV antigens in the HPV vaccine. The boxes represent the length of the amino acid sequences from the N-terminus to the C-terminus. Figure 6B The multiple HLA class I-binding peptides that define the HPV vaccine-specific set of T cell responses from 2 patients. Process to identify multiple HLA-binding peptides from two patients: HLA sequences from the patients marked as 4-digit HLA genotype to the right of the patient ID. The lo-amino acid location of the 54 and 91 epitopes that can bind to patient HLA 12-11 and patient 14-5 (PEPI1+) respectively are illustrated with lines. PEPI2 represents peptides selected from PEPI1+ that can bind to multiple HLAs of a patient (PEPI2+). PEPI3 represents peptides that can bind to a patient's HLA éé3 (PEPI3+). PEPI4 represents peptides that can bind to ^4 HLA of a patient (PEPI4+). PEPI5 represents peptides that can bind to a patient's HLA éé5 (PEPI5+). PEPI6 represents the peptides that can bind to 6 HLA of a patient (PEPI6). Figure 6C The multiple HLA class I-binding peptides that define the HPV vaccine-specific set of T cell responses from 2 patients. The vaccine-specific PEPI3+ pool of DNA from two patients characterizes their vaccine-specific T cell responses. Figure 7 Correlation between PEPI3+ ^1 score and CTL response rates of peptide targets determined in clinical trials. Figure 8 Correlation between the PEPI3+ ul score and the clinical immune response rate (IRR) of immunotherapy vaccines. Dotted lines: 95% confidence band. Figure 9 Correlation between PEPI3+ score =2 and disease control rate (DCR) of immunotherapy vaccines. Dotted lines: 95% confidence band. Figure 10 Example of peptide interest point analysis: PRAME antigen points of interest in 433 patients from the model population. On the y-axis are the 433 patients of the model population, on the x-axis is the amino acid sequence of the PRAME antigen (CTA). Each data point represents a PEPI presented by ^3 HLA class I from a patient starting at the specified amino acid position. The two most frequent PEPIs (referred to as best EPIs) of the PRAME antigen are highlighted in dark gray (peptide hotspots = PEPI hotspots). Figure 11 CTA expression curve calculated by analysis of tumor-specific antigen (CTA) expression frequency data in human breast cancer tissues. (Cell line data were not included). Figure 12A Antigen expression distribution for breast cancer based on calculation of multiple antigen responses from expression frequencies of the 10 different selected CTAs. Non-cumulative distribution to calculate the expected value for the amount of antigens expressed (AG50). This value shows that 6.14 vaccine antigens are likely to be expressed by breast tumor cells. Figure 12B Antigen expression distribution for breast cancer based on calculation of multiple antigen responses from expression frequencies of the 10 different selected CTAs. Cumulative distribution curve of the minimum amount of expressed antigens (CTA expression curve). This shows that at least 4 vaccine antigens will be expressed with 95% probability in the breast cancer cell (AG95). Figure 13A Distribution of PEPI-represented antigens (breast cancer vaccine-specific CTA antigens with <1 PEPI, designated "AP") within the model population (n=433) for breast cancer vaccine. Non-cumulative distribution of PAs where the average amount of PAs is: PA5O=5.3O, which means that on average almost 6 CTAs will have PEPI in the model population. Figure 13B Distribution of PEPI-represented antigens (breast cancer vaccine-specific CTA antigens with <1 PEPI, designated "AP") within the model population (n=433) for breast cancer vaccine. Cumulative distribution curve of the minimum amount of PA in the model population (n=433). This shows that at least one vaccine antigen will have PEPT in 95% of the model population (n=433) (AP95=1). Figure 14A Distribution of expressed antigens represented by PEPI (tumor-expressed breast cancer vaccine-specific CTA antigens, for which <1 PEPI is predicted, termed "AGP") within the model population (n=433) calculated with rates of CTA expression for breast cancer. Non-cumulative distribution of AGP where the expected value for the amount of expressed CTA represented by PEPI is AGP50=3.37. AGP50 is a measure of the efficacy of the described breast cancer vaccine in targeting the breast tumor in an unselected patient population. AGP50 = 3.37 means that at least 3 CTAs from the vaccine are likely to be expressed by breast tumor cells and display PEPI in the model population. Figure 14B Distribution of expressed antigens represented by PEPI (tumor-expressed breast cancer vaccine-specific CTA antigens, for which <1 PEPI is predicted, termed "AGP") within the model population (n=433) calculated with rates of CTA expression for breast cancer. The cumulative distribution curve of the minimum amount of AGP in the model population (n=433) shows that at least 1 of the vaccine CTAs will have PEPI in 92% of the population and the remaining 8% of the population will probably not have PEPI. AGP not at all (AGP95=0, AGP92=1). Figure 15 CTA expression curve calculated by analysis of tumor-specific antigen (CTA) expression frequency data in human colorectal cancer tissues. (Cell line data were not included). Figure 16A Antigen expression distribution for colorectal cancer based on calculation of multiple antigen responses from expression frequencies of the 7 different selected CTAs. Non-cumulative distribution to calculate the expected value for the amount of vaccine antigens expressed in colorectal cancers (AG50). This value shows that 4.96 vaccine antigens are likely to be expressed by colorectal tumor cells. Figure 16B Antigen expression distribution for colorectal cancer based on calculation of multiple antigen responses from expression frequencies of the 7 different selected CTAs. Cumulative distribution curve of the minimum amount of expressed antigens (CTA expression curve). This shows that at least 3 antigens will be expressed with 95% probability in the colorectal cancer cell (AG95). Figure 17A Distribution of PEPI-represented antigens (CTA colorectal cancer vaccine-specific antigens predicted for <1 PEPI, designated "AP") within the model population (n=433) for colorectal cancer. Non-cumulative distribution of AP where the average amount of AP is: AP50=4.73, which means that on average 5 CTA will be represented by PEPI in the model population. Figure 17B Distribution of PEPI-represented antigens (CTA colorectal cancer vaccine-specific antigens predicted for <1 PEPI, designated "AP") within the model population (n=433) for colorectal cancer. Cumulative distribution curve of the minimum amount of PA in the model population (n=433). This shows that 2 or more antigens will be represented by PEPI in 95% of the model population (n=433) (AP95=2). Figure 18A Distribution of expressed antigens represented by PEPI (tumor-expressed colorectal cancer vaccine-specific CTA antigens, for which <1 PEPI is predicted, termed "AGP") within the model population (n=433) calculated with rates of CTA expression for colorectal cancer. A: non-cumulative distribution of AGP where the expected value for the amount of expressed CTA represented by PEPI is AGP50=2.54. AGP50 is a measure of the efficacy of the described colorectal cancer vaccine in targeting colorectal tumors in an unselected patient population. AGP50 = 2.54 means that probably at least 2-3 CTAs from the vaccine will be expressed by colorectal tumor cells and will present PEPI in the model population. Figure 18B Distribution of expressed antigens represented by PEPI (tumor-expressed colorectal cancer vaccine-specific CTA antigens, for which <1 PEPI is predicted, termed "AGP") within the model population (n=433) calculated with rates of CTA expression for colorectal cancer. The cumulative distribution curve of the minimum amount of AGP in the model population (n=433) shows that at least 1 of the vaccine CTAs will be expressed and will also present PEPI in 93% of the population (AGP93=1). Figure 19 Scheme showing exemplary amino acid positions in overlapping HLA class I and HLA class II binding epitopes in a 30-mer peptide. Figure 20 Antigenicity of PolyPEPI1018 CRC vaccine in a general population. The antigenicity of PolyPEPI1018 in a subject is determined by the AP count, which indicates the amount of vaccine antigens that induce T cell responses in a subject. The AP count of PolyPEPI1018 was determined in each of the 433 subjects in the model population using the PEPI test, and then the AP50 count was calculated for the model population. The AP50 of PolyPEPI1018 in the model population is 4.73. The mean number of immunogenic antigens (ie, antigens with <1 PEPI) on PolyPEPI1018 in a general population is 4.73. Abbreviations: AP = antigens with <1 PEPI. Left panel: cumulative distribution curve. Right panel: different distribution curve. Figure 21 Efficacy of PolyPEPI1018 CRC vaccine in a general population. Vaccine-induced T cells can recognize and kill tumor cells if the tumor cell presents a PEPI in the vaccine. The amount of AGP (PEPI-expressed antigens) is an indicator of vaccine efficacy in an individual, and depends on the potency and antigenicity of P0IÍPEPIIOI8. The mean number of immunogenic CTAs (ie AP [antigens expressed with <1 PEPI]) in P0IÍPEPIIOI8 is 2.54 in the model population. The probability that PolyPEPI1018 will induce T-cell responses against multiple antigens in one subject (ie, mAGP) in the model population is 77%. Figure 22 Probability of vaccine antigen expression in tumor cells from patient XYZ. There is a greater than 95% probability that 5 of the 12 target antigens in the vaccination regimen are expressed in the patient's tumor. Therefore, the 12-peptide vaccines together can induce immune responses against at least 5 ovarian cancer antigens with a probability of 95% (AGP95). There is an 84% chance that each peptide will induce immune responses in patient XYZ. AGP50 is the mean (expected value) =7.9 (it is a measure of the efficacy of the vaccine in attacking patient XYZ's tumor). Figure 23 MRI findings of patient XYZ treated with the personalized vaccine (PIT). This highly pretreated late-stage ovarian cancer patient had an unexpected target response after treatment with the PIT vaccine. These MRI findings suggest that the PIT vaccine in conjunction with chemotherapy significantly reduced tumor burden. The patient is now continuing treatment with the PIT vaccine. Figure 24 Probability of expression of vaccine antigen in tumor cells of patient ABC. There is a probability of more than 95% that 4 of the 13 target antigens in the vaccination are expressed in the patient's tumor. Therefore, the 12-peptide vaccines together can induce immune responses against at least 4 breast cancer antigens with a probability of 95% (AGP95). There is an 84% chance that each peptide will induce immune responses in patient ABC. AGP50 is the mean (expected value) of the discrete probability distribution = 6.45 (it is a measure of the efficacy of the vaccine in attacking patient ABC's tumor). DESCRIPTION OF THE SEQUENCES SEQ ID NO: 1 to 20 present the 9mer T-cell epitopes described in Table 17. SEQ ID NOs: 21 to 40 present the 9mer T cell epitopes described in Table 20. SEQ ID NOs 41 to 60 present the 15mer T cell epitopes described in Table 17. SEQ ID NOs 61 to 80 present the 15mer T cell epitopes described in Table 20. SEQ ID NOs: 81 to 111 present the breast cancer vaccine peptides described in Table 18a. SEQ ID NOs 112 to 142 present the colorectal cancer vaccine peptides described in Table 21a. SEQ ID NOs 143 to 158 present antigens associated with breast cancer, colorectal cancer and / or ovarian cancer. SEQ ID NOs 159 to 171 present the additional peptide sequences described in Table 10. SEQ ID NOs 172 to 194 present additional 9mer T cell epitopes described in Table 17. SEQ ID NOs 195 to 233 present additional 15mer T cell epitopes described in Table 17. SEQ ID NOs 234 to 250 present additional 9mer T cell epitopes described in Table 20. SEQ ID NOs 251 to 271 present additional 15mer T cell epitopes described in Table 20. SEQ ID NOs: 272 to 301 present the 9mer T cell epitopes described in Table 23. SEQ ID NO: 302 to 331 present the 15 mor T cell epitopes described in Table 23. SEQ ID NOs: 332 to 346 present the ovarian cancer vaccine peptides set forth in Table 24. SEQ ID NOs: 347 to 361 present additional breast cancer, colorectal cancer and / or ovarian cancer associated antigens. SEQ ID NOs: 362 to 374 present the custom vaccine peptides designed for patient XYZ described in Table 38. SEQ ID NOs: 375 to 386 present the custom designed vaccine peptides for the ABC patient described in Table 41. SEQ ID NOs 387 to 434 present additional 9mer T cell epitopes described in Table 32. SEQ ID NOs: 435 to 449 present the additional breast cancer vaccine peptides described in Table 18a. DETAILED DESCRIPTION HLA genotypes HLAs are encoded by the most polymorphic genes in the human genome. Each person has one maternal and one paternal allele for the three HLA class I molecules (HLA-A*, HLA-B*, HLA-C*) and four HLA class II molecules (HLA-DP*, HLA- DQ*, HLA-DRB1*, HLA-DRB3* / 4* / 5*). In practice, each person expresses a different combination of 6 HLA class I and 8 HLA class II molecules that present different epitopes of the same protein antigen. The function of HLA molecules is to regulate T cell responses. However, until now it was unknown whether a person's HLAs regulate T cell activation. The nomenclature used to designate the amino acid sequence of the HLA molecule is as follows: gene name*allele:protein number, which, for example, can be seen as: HLA-A*02:25. In this example, "02" refers to the allele. In most cases, alleles are defined by serotypes, which means that the proteins of a given allele will not react with each other in serological tests. Protein numbers ("25" in the example above) are assigned consecutively as the protein is discovered. A new protein number is assigned for any protein with a different amino acid sequence (eg, even a change of one amino acid in the sequence is considered a different protein number). Other information on the nucleic acid sequence of a given locus can be attached to the HLA nomenclature, but this information is not necessary for the methods described herein. The HLA class I genotype or the HLA class II genotype of an individual may refer to the actual amino acid sequence of each HLA class I or class II in an individual, or it may refer to nomenclature, such as described above, which designates, minimally, the allele and protein number of each HLA gene. An HLA genotype can be determined using any suitable method. For example, the sequence can be determined through sequencing of HLA gene loci using methods and protocols known in the art. Alternatively, an individual's HLA pool may be stored in a database and accessed using methods known in the art. Some subjects may have two HLA alleles encoding the same HLA molecule (eg two copies for HLA-A*02:25 in case of homozygosity). The HLA molecules encoded by these alleles all bind to the same T cell epitopes. For the purposes of this description "binding to at least two HLA molecules from the subject", as used herein, includes binding to HLA molecules encoded by two identical HLA alleles in a single subject. In other words, "bind to at least two HLA molecules from the subject" and the like can be expressed otherwise as "bind to HLA molecules encoded by at least two HLA alleles from the subject". polypeptides The description refers to polypeptides that are derived from CTA and that are immunogenic for a high proportion of the human population. As used herein, the term "polypeptide" refers to a full-length protein, a portion of a protein, or a peptide characterized as a chain of amino acids. As used herein, the term "peptide" refers to a short polypeptide comprising between 2, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 and 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55 or 60 amino acids. The terms "fragment" or "fragment of a polypeptide," as used herein, refer to an amino acid chain or amino acid sequence that is typically reduced in length relative to the reference polypeptide or a reference polypeptide and that it comprises, on the common part, an amino acid sequence identical to the reference polypeptide. Said fragment, according to the description, can be included, where appropriate, in a larger polypeptide of which it is a constituent. In some cases, the fragment may comprise the full length of the polypeptide, for example, where the entire polypeptide, such as a 9 amino acid peptide, is a single T cell epitope. In some cases, the fragments referred to herein may be of between 2, 3, 4, 5, 6, 7, 8, 9 and 20, 25, 30, 35, 40, 45 or 50 amino acids. As used herein, the term "epitope" or "T cell epitope" refers to a contiguous amino acid sequence found within a protein antigen that possesses a binding affinity for (is capable of binding to) ) one or more HLAs. An epitope is HLA- and antigen-specific (HLA-epitope pairs, predicted by known methods), but not subject-specific. An epitope, T-cell epitope, polypeptide, polypeptide fragment, or composition comprising a polypeptide or fragment thereof is "immunogenic" for a specific human subject if it is capable of inducing a T-cell response (a cytotoxic T-lymphocyte response or a helper T-lymphocyte response) in that subject. In some cases, the T helper cell response is a ThL-type helper T cell response In some cases, an epitope, a T cell epitope, a polypeptide, a fragment of a polypeptide, or a composition comprising a polypeptide or a fragment of this is "immunogenic" for a specific human subject if it is more likely to induce a T-cell response or an immune response in the subject than a different T-cell epitope (or, in some cases, two different T-cell epitopes each). one) capable of binding to a single HLA molecule from the subject. The terms "T cell response" and "immune response" are used interchangeably herein and refer to the activation of T cells and / or the induction of one or more effector functions following recognition of one or more T cell pairs. HLA-epitope binding. In some cases, an "immune response" includes an antibody response since HLA class II molecules stimulate helper responses that are involved in the induction of CTL responses and long-lasting antibody responses. Effector functions include cytotoxicity, cytokine production and proliferation. In accordance with the present description, an epitope, a T cell epitope or a fragment of a polypeptide is immunogenic for a specific subject if it is capable of binding to at least two, or in some cases at least three, HLA class I or at least two, or in some cases at least three or at least four. HLA class II of the subject. For the purpose of the present description, we have coined the term "personal epitope" or "PEPI" to distinguish subject-specific epitopes from HLA-specific epitopes. A "PEPI" is a polypeptide fragment consisting of a contiguous amino acid sequence of the polypeptide that is a T cell epitope capable of binding one or more HLA class I molecules from a specific human subject. In other instances, a "ΡΕΡΓ' is a fragment of a polypeptide consisting of a contiguous amino acid sequence of the polypeptide that is a T cell epitope capable of binding one or more HLA class I molecules from a specific human subject. In other words, a "PEPI" is a T-cell epitope that is recognized by a specific individual's HLA pool and is therefore subject-specific in addition to HLA and antigen.Unlike an "epitope", which is specific only to HLA and antigen, PEPIs are individual-specific because different individuals have different HLA molecules that each bind to different T cell epitopes This subject specificity of PEPIs allows for the development of cancer vaccines "ΡΕΡΙ1", as used herein, refers to a peptide, or a fragment of a polypeptide, that can bind to an HLA class I molecule (or, in specific contexts, an HLA class I molecule). of HLA class II) of an individual. "PEPI1+" refers to a peptide, or a fragment of a polypeptide, that can bind to one or more HLA class I molecules of an individual. "PEPI2" refers to a peptide, or a fragment of a polypeptide, that can bind to two HLA class I (or II) molecules of an individual. "PEPI2+" refers to a peptide, or a fragment of a polypeptide, that can bind to two or more HLA class I (or II) molecules of an individual, that is, a fragment identified according to a method of the description. "PEPI3" refers to a peptide, or a fragment of a polypeptide, that can bind to three HLA class I (or II) molecules in an individual. "PEPI3+" refers to a peptide, or a fragment of a polypeptide, that can bind to three or more HLA class T (or TT) molecules from an individual. "PEPI4" refers to a peptide, or a fragment of a polypeptide, that can bind to four HLA class I (or II) molecules of an individual. "PEPI4+" refers to a peptide, or a fragment of a polypeptide, that can bind to four or more HLA class I (or II) molecules of an individual. "PEPI5" refers to a peptide, or a fragment of a polypeptide, that can bind to five HLA class I (or II) molecules in an individual. "PEPI5+" refers to a peptide, or a fragment of a polypeptide, that can bind to five or more HLA class I (or II) molecules in an individual. "PEPI6" refers to a peptide, or a fragment of a polypeptide, that can bind to all six HLA class I (or six HLA class II) molecules in an individual. Generally speaking, epitopes displayed by HLA class I molecules are about nine amino acids in length and epitopes displayed by HLA class II molecules are about fifteen amino acids in length. For purposes of the present disclosure, however, an epitope may be more or less than nine (for HLA class I) or fifteen (for HLA class II) amino acids in length, so long as the epitope is capable of binding HLA. . For example, an epitope that is capable of binding to HLA class I can be between 7, 8 or 9 and 9, 10 or 11 amino acids in length. An epitope that is capable of binding HLA class II may be between 13, 14 or 15 and 15, 16 or 17 amino acids in length. A given HLA from a subject will only present to T cells a limited number of different peptides produced by processing protein antigens on an APC. As used herein, "display" or "present", when used in connection with HLA, refers to the binding between a peptide (epitope) and an HLA. In this sense, "displaying" or "presenting" a peptide is synonymous with "binding" to a peptide. Using techniques known in the art it is possible to determine the epitopes that will bind to a known HLA. Any suitable method may be used, so long as the same method is used to determine multiple HLA-epitope binding pairs that are directly compared. For example, biochemical analysis can be used. It is also possible to use lists of epitopes known to bind via a given HLA. It is also possible to use predictive or modeling software to determine which epitopes can be bound by a given HLA. Examples are provided in Table 1. In some cases, a T cell epitope is capable of binding a given HLA if it has an IC50 or predicted IC50 of less than 5000 nM, less than 2000 nM, less than 1000 nM, or less than 500 nM. Table 1 - Exemplary software to determine epitope-HLA binding WEB MANAGEMENT TOOLS EPITOPE PREDICTION BIMAS, NIH www-bimas.cit.nih.gov / molbio / hla_bind / PPAPROC, Tubingen Univ. MHCPred, Edward Jenner Inst. of Vaccine Res. EpiJen, Edward Jenner Inst. of http: / / www.ddg-pharmfac.net / epijen / EpiJen / EpiJen.htm Vaccine Res. NetMHC, Center for Biological http: / / www.cbs.dtu.dk / services / NetMHC / Sequence Analysis SVMHC, Tubingen Univ. http: / / abi.inf.uni-tuebingen.de / Services / SVMHC / SYFPEITHI, Biomedicalhttp: / / www.syfpeithi.de / bin / MHCServer.dll / EpitopePredictio Informatics, Heidelberg n.htm ETK EPITOOLKIT, Tubingenhttp: / / etk.informatik.uni-tuebingen.de / epipred / Univ. PREDEP, Hebrew Univ. Jerusalem http: / / margalit.huji.ac.il / Teppred / mhc-bind / index.html RANKPEP, MIF Bioinformatics http: / / bio.dfci.harvard.edu / RANKPEP / IEDB, Immune Epitope Database http: / / tools.immuneepitope.org / main / html / tcell_tools.html WEB ADDRESS DATABASES MHCBN EPITOPES, Institute of Microbial http: / / www.imtech.res.in / raghava / mhcbn / Technology, Chandigarh, INDIA SYFPEITHI, Biomedicalhttp: / / w ww. syfpeithi .de / Informatics, Heidelberg Antilen, Edward Jenner Inst. of http: / / www.ddg- Vaccine Res. phamifac.net / antijen / Antilen / antijenhomepage.htm EPIMHC database of MHChttp: / / immunax.dfci.harvard.edu / epimhc / ligands, MIF Bioinformatics IEDB, Immune Epitope Database http: / / www.iedb.org / In some embodiments, the peptides of the disclosure may comprise or consist of one or more fragments of one or more CTAs. CTAs are not normally expressed beyond embryonic development in healthy cells. In healthy adults, CTA expression is limited to male germ cells that do not express HLA and cannot present antigens to T cells. Therefore, CTAs are considered expressing neoantigens when expressed on cancer cells. CTAs are a good option for cancer vaccine targets, because their expression is (i) specific for tumor cells, (ii) more frequent in metastases than in primary tumors, and (iii) is conserved between metastases from the same patient (Gajewski ed. Targeted Therapeutics in Melanoma. Springer, New York. 2012). The peptides of the description may comprise or consist of one or more fragments of one or more breast cancer-associated antigens selected from SPAG9 (SEQ ID NO: 143), AKAP-4 (SEQ ID NO: 144), BORIS (SEQ ID NO: 145), NY-SAR-35 (SEQ ID NO: 146), NY-BR-1 (SEQ ID NO: 147), SURVIVIN (SEQ ID NO: 148), MAGE-A11 (SEQ ID NO: 149) , PRAME (SEQ ID NO: 150), MAGE-A9 (SEQ ID NO: 151), HOM-TES-85 (SEQ ID NO: 152), PIWIL-2 (SEQ ID NO: 349), EpCAM (SEQ ID NO : 154), HIWI (SEQ ID NO: 350), PLU-1 (SEQ ID NO: 351), TSGA10 (SEQ ID NO: 351), ODF-4 (SEQ ID NO: 352), SP17 (SEQ ID NO: 354), RHOXF-2 (SEQ ID NO: 355) and NY-ESO-1 (SEQ ID NO: 356); one or more ovarian cancer-associated antigens selected from PIWIL-4 (SEQ ID NO: 357), WT1 (SEQ ID NO: 358), EpCAM (SEQ ID NO: 154), BORIS (SEQ ID NO: 145), AKAP -4 (SEQ ID NO: 144), OY-TES-1 (SEQ ID NO: 359), SP17 (SEQ ID NO: 354), PIWIL-2 (SEQ ID NO: 349), PIWIL-3 (SEQ ID NO : 360), SPAG9 (SEQ ID NO: 143), PRAME (SEQ ID NO: 150), HIWI (SEQ ID NO: 350), SURVIVIN (SEQ ID NO: 148) and AKAP-3 (SEQ ID NO: 361) ; and / or one or more colorectal cancer associated antigens selected from TSP50 (SEQ ID NO: 153), EpCAM (SEQ ID NO: 154), SPAG9 (SEQ ID NO: 143), CAGE1 (SEQ ID NO: 155), FBXO39 (SEQ ID NO: 156), SURVIVIN (SEQ ID NO: 148), MAGE-A8 (SEQ ID NO: 157), MAGE-A6 (SEQ ID NO: 158), LEMD1 (SEQ ID NO: 348) and MAGE-A3 (SEQ ID NO: 347). In some cases, the peptide comprises or consists of one or more amino acid sequences selected from SEQ ID NO: 41-80 or from SEQ ID NO: 41-80, 195-233, 251-271 and 302-331 that are optimized for T cell activation / binding to all HLA types across the population. In some cases, the amino acid sequence is flanked at the N- and / or C-terminus by additional amino acids that are not part of the target polypeptide antigen sequence, in other words, that are not the same sequence of consecutive amino acids found adjacent to each other. the selected fragments on the target polypeptide antigen. In some cases, the sequence is flanked by up to 41, 35, 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 additional amino acid at the N-terminus and / or C or between the target polypeptide fragments. In other cases, each polypeptide consists of a fragment of a target polypeptide antigen or consists of two or more such fragments arranged end-to-end (arranged sequentially in the peptide end-to-end) or overlapping in a single peptide (where two or more of the fragments comprise partially overlapping sequences, eg, where two PEPIs in the same polypeptide are 50 amino acids apart). When fragments of different polypeptides or different regions of the same polypeptide are brought together in a genetically modified peptide, there is a possibility that neoepitopes will be generated around the junction. Such neoepitopes encompass at least one amino acid of each fragment on both sides of the junction, and may be referred to herein as linker amino acid sequences. Neoepitopes can induce unwanted T cell responses against healthy cells (autoimmunity). The polypeptides can be designed, or the polypeptides can be tested, to avoid, eliminate, or minimize neoepitopes that correspond to a fragment of a protein expressed in normal healthy human cells and / or neoepitopes that are capable of binding to at least two, in some cases at least three or at least four HLA class I molecules from the subject, or in some cases at least two, at least three, four or five HLA class II molecules from the subject. In some cases, the peptide is designed, or the polypeptide is tested, to eliminate polypeptides that have a binding neoepitope that is capable of binding in more than a threshold percentage of human subjects in an intent-to-treat, target, or model population. at least two HLA class I molecules expressed by individual subjects in the population. In some cases, the threshold is 20%, 15%, 10%, 5%, 2%, 1%, or 0.5% of that population. Alignment can be determined using known methods, such as BLAST algorithms. Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). The presence in an immunotherapy or vaccine composition of at least two polypeptide fragments (epitopes) that can bind to at least three HLA class I from an individual (<2 PEPT3+) predicts a clinical response. In other words, if <2 PEPT3+ can be identified within the polypeptides of the active ingredient of an immunotherapy or vaccine composition, an individual is likely to be a clinical responder. The at least two multi-HLA binding PEPIs of the polypeptides of the composition may target a single antigen (e.g., a polypeptide vaccine comprising two multi-HLA binding PEPIs derived from a single tumor-associated antigen, vaccine target) or may target different antigens (e.g., a polypeptide vaccine comprising one multi-HLA-binding PEPI derived from a tumor-associated antigen, and a second multi-HLA-binding PEPI derived from a tumor-associated antigen). different tumor-associated antigen). Without wishing to be bound by theory, the inventors believe that one reason for the increased likelihood of clinical benefit from a vaccine / immunotherapy comprising at least two multi-HLA binding PEPIs is that diseased cell populations, such as cancerous or tumor cells or cells infected by viruses or pathogens such as HIV, are usually heterogeneous both within and between the affected subjects. A specific cancer patient, for example, may or may not express or overexpress a particular cancer-associated target polypeptide antigen of a vaccine or their cancer may comprise heterogeneous cell populations, some of which (over)express the antigen and some of which of which not. Furthermore, the likelihood of developing resistance decreases when a vaccine / immunotherapy includes or targets more multi-HLA binding PEPIs because the patient is less likely to develop resistance to the composition through mutation of the targeted PEPIs. Currently, most immunotherapy and vaccine compositions target only a single polypeptide antigen. However, in accordance with the present disclosure, it is in some cases beneficial to provide a pharmaceutical composition directed at two or more different polypeptide antigens. For example, most cancers or tumors are heterogeneous, meaning that cancer or tumor cells from a subject (over)express different antigens. Tumor cells from different cancer patients also express different combinations of tumor-associated antigens. The cancer immunogenic compositions that are most likely to be effective are those that target multiple antigens expressed by the tumor, and thus more cancer or tumor cells, in an individual human subject or in a population. The beneficial effect of combining multiple best EPIs in a single treatment (administration of one or more pharmaceutical compositions that together comprise multiple EPIs) can be illustrated by the personalized vaccine polypeptides described in Examples E5 and 16 below. Exemplary CTA expression probabilities in ovarian cancer are as follows: BAGE: 30%; MAGE A9: 37%; MAGE A4: 34%; MAGE A10: 52%. If patient XYZ were treated with a vaccine comprising PEPI only in BAGE and MAGE A9, the probability of having a mAGP (multiple antigens expressed with PEPI) would be 11%. If patient XYZ were treated with a vaccine comprising only PEPI for MAGE A4 and MAGE A10 CTAs, the probability of having a multiAGP would be 19%. However, if a vaccine contains all 4 of these CTAs (BAGE, MAGE A9, MAGE A4, and MAGE A10), the probability of having a mGP would be 50%. In other words, the effect would be greater than the combined mAGP odds for both PEPI treatments (mGP odds for BAGE / MAGE + mAGP odds for MAGE A4 and MAGE A10). Patient XYZ's PIT vaccine described in Example 21 contains an additional 9 PEPIs and thus the probability of having a mAGP is greater than 99.95%. Likewise, the probabilities of exemplary CTA expression in breast cancer are as follows: MAGE C2: 21%; MAGE Al: 37%; SPC1: 38%; MAGE A9: 44%. Treatment of patient ABC with a vaccine comprising PEPI alone at MAGE C2: 21% and MAGE Al has a probability of mAGP of 7%.Treatment of patient ABC with a vaccine comprising PEPI only in SPC1: 38%; MAGE A9 has a mAGP probability of 11%. Treatment of patient ABC with a vaccine comprising PEPI in MAGE C2: 21%; MAGE Al: 37%; SPC1: 38%; MAGE A9 has a mGP probability of 44% (44 > 7 + 11). Patient ABC's PIT vaccine described in Example 22 contains an additional 8 PEPIs and thus the probability of having a mAGP is greater than 99.93%. Accordingly, in some instances, the polypeptide or panel of polypeptides of the disclosure or a polypeptide of the active ingredient of a pharmaceutical composition or kit of the disclosure may comprise or consist of any combination of at least 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 fragments of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 or more of the antigens associated with cancer, or CTA, such as the CTA discussed above. Each fragment comprises or consists of a different target epitope having an amino acid sequence selected from SEQ ID NO: 1-40; selected from SEQ ID NO: 1 to 20; selected from SEQ ID NO: 21 to 40; selected from SEQ ID NOs: 1-20, 24 and 172-194; selected from SEQ ID NO: 21-40 and 234-250; selected from SEQ ID NO: 272-301; selected from SEQ ID NOs: 1-40, 172-194 and 234-250; selected from SEQ ID NOs: 21-40, 234-250 and 272-301; selected from SEQ TD NO: 1-20, 24, 172-194 and 272-301; selected from SEQ ID NO: 1-40, 172-194, 234-250 and 272-301; selected from SEQ ID NOs: 41-60, 64 and 195-233; selected from SEQ ID NOs: 61-80 and 251-271; selected from SEQ ID NO: 302-331; selected from SEQ ID NOs: 41-80, 195-233 and 251-271; selected from SEQ ID NO: 61-80, 251-271 and 302 to 331; selected from SEQ ID NO: 41-60, 64, 191-233 and from 302 to 331; selected from SEQ ID NOs: 41-80, 195-233, 251-271 and 332-346; selected from SEQ ID NOs: 1-20, 24, 41-60, 64, 172-194 and 195-233; selected from SEQ ID NO: 21-40, 61-80, 234-250 and 251-271; selected from SEQ ID NO: 271-331; selected from SEQ ID NOs: 1-80, 172-194, 195-233, 234-250 and 251-271; selected from SEQ ID NOs: 21-40, 61-80, 234-250, 251-271, 272-301 and 302-331; selected from SEQ ID NO: 1-80, 172-233, 234-271 and 272-331; selected from SEQ ID NOs: 81-111 and 435-449; selected from SEQ ID NO: 112-142; selected from SEQ ID NO: 332-346; selected from SEQ ID NO: 81-142; selected from SEQ ID NO: 112-142 and 332-346; selected from SEQ ID NOs: 81-111, 435-449 and 332-346; selected from SEQ ID NO: 81-142 and 332-346; selected from SEQ ID NOs: 41-60, 64, 81-111, 435-449 and 195-233; selected from SEQ ID NOs: 61-80, 112-142 and 251-271; selected from SEQ ID NO: 302-346; selected from SEQ ID NOs: 41-142, 195-233 and 251-271; selected from SEQ ID NOs: 61-80, 112-142, 251-271 and 302-346; selected from SEQ ID NOs: 41-60, 64, 81-111, 435-449, 195-233 and 302-346; selected from SEQ ID NO: 41-142, 195-233, 251-271 and 302-346; selected from SEQ ID NOs: 1-20, 24, 41-60, 64, 81-111, 435-449 and 172-233; selected from SEQ ID NO: 21-40, 61-80, 112-142 or 234-271; selected from SEQ ID NO: 272-346; selected from SEQ ID NO: 1-142 and 172-271; selected from SEQ ID NOs: 21-40, 61-80, 112-142 and 234-346; selected from SEQ ID NO: 1-20, 24, 41-60, 64, 81-111, 435-449, 172-233 and 272 to 346; selected from SEQ ID NO: 1-142 and 172-346; or selected from SEQ ID NO: 1 to 2 or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or SEQ ID NO: from 20 to 21 or 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 or 39; or a different amino acid sequence selected from SEQ ID NO: 41 to 80, SEQ ID NO: 41 to 60, SEQ ID NO: 61-80; or SEQ ID NO: from 41 to 42, to 43, to 44, to 45, to 46, to 47, to 48 or to 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 or 59, SEQ ID NO: 60 to 61, to 62, to 63, to 64, to 65, to 66, to 67, to 68, to 69, to 70, to 71, to 72, to 73, to 74, to 75 , at 76, at 77, at 78 or at 79; a different amino acid sequence selected from SEQ ID NO: 81 to 142; selected from SEQ ID NO: 81 to 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102 , 103, 105, 106, 107, 108, 109, 110 or 111; selected from SEQ ID NO: 81 to 105; selected from SEQ ID NO: 99, 100, 92, 93, 101, 103, 104, 105 and 98; selected from SEQ ID NO: 112 to 142; selected from SEQ TD NO: 112 to 113, 114, 115, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141 or 142; selected from SEQ ID NO: 112 to 134; selected from SEQ ID NO: 121, 124, 126, 127, 130, 131, 132, 133 and 134; selected from SEQ ID NO: from 1 to 2 or from 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,18, 19 or SEQ ID NO: from 20 to 21 or 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 or 39;or a different amino acid sequence selected from SEQ ID NO: 41 to 80, SEQ ID NO: 41 to 60, SEQ ID NO: 61-80; or SEQ ID NO: from 41 to 42, to 43, to 44, to 45, to 46, to 47, to 48 or to 49, 50, 51, 52, 53, 54, 55, 56, 57, 58 or 59, SEQ ID NO: 60 to 61, to 62, to 63, to 64, to 65, to 66, to 67, to 68, to 69, to 70, to 71, to 72, to 73, to 74, to 75 , at 76, at 77, at 78 or at 79; a different amino acid sequence selected from SEQ ID NO: 81 to 142; selected from SEQ ID NO: 81 to 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102 , 103, 105, 106, 107, 108, 109, 110 or 111; selected from SEQ ID NO: 81 to 105; selected from SEQ ID NO: 99, 100, 92, 93, 101, 103, 104, 105 and 98; selected from SEQ ID NO: 112 to 142; selected from SEQ ID NO: 112 to 113, 114, 115, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134 , 135, 136, 137, 138, 139, 140, 141 or 142; selected from SEQ ID NO: 112 to 134; selected from SEQ ID NO: 121, 124, 126, 127, 130, 131, 132, 133 and 134; selected from SEQ ID NO: 130, 121, 131, 124, 134, 126; selected from SEQ ID NO: 435-449; or selected from any of these groups of sequences, excluding SEQ ID NO: 12, 32, 19 and / or 39, and / or SEQ ID NO: 21, 41, 23 and / or 43 and / or SEQ ID NO: 172, 177, 195 and / or 203, and / or SEQ ID NO: 1, 41 and / or 197, and / or SEQ ID NO: 4, 44 and / or 201, and / or SEQ ID NO: 1, 4, 44 , 197 and / or 201, and / or SEQ ID NO: 1, 41, 197, 184 and / or 212, and / or SEQ ID NO: 3, 43 and / or 200, and / or SEQ ID NO: 3, 43, 200, 7 and / or 47, and / or SEQ ID NO: 10, 50 and / or 220, and / or SEQ ID NO: 24, 64 and / or 202, and / or SEQ ID NO: 6, 46 and / or 209, and / or SEQ ID NO: 182, 210, 185 and / or 213, and / or SEQ ID NO: 14, 54, 225 and 226, and / or SEQ ID NO: 190, 218, 11, 51 and / or 219, and / or SEQ ID NO: 12, 224 and / or 52, and / or SEQ ID NO: 192, 227 and / or 228, and / or SEQ ID NO: 17, 229, 230 and / or or 57, and / or SEQ ID NO: 21, 252, 61 and / or 253, and / or SEQ ID NO: 23, 63 and / or 256, and / or SEQ ID NO: 21, 252, 61, 253, 23, 63 and / or 256, and / or SEQ ID NO: 237 and / or 238, and / or SEQ ID NO: 26 and / or 240, and / or SEQ ID NO: 242, 244, 263 and / or 265 , and / or SEQ ID NO: 29, 69 and / or 259, and / or SEQ ID NO: 24, 64 and / or 255, and / or SEQ ID NO: 236, 257 and / or 258, and / or SEQ ID NO: 2 7, 67, 241 and / or 262, and / or SEQ ID NO: 252, 249 and / or 264, and / or SEQ ID NO: 35, 250 and / or 75, and / or SEQ ID NO: 252, 249 , 264, 35, 250 and / or 75, and / or SEQ ID NO: 36, 266 and / or 76, and / or SEQ ID NO: 36, 266, 76, 39 and / or 79, and / or SEQ ID NO: 38, 268 and / or 78, and / or SEQ ID NO: 38, 268, 78, 246 and / or 270, and / or SEQ ID NO: 245, 269 and / or 248, and / or SEQ ID NO : 245, 269, 248, 40 and / or 80, and / or SEQ ID NO: 272, 302, 281 and / or 311, and / or SEQ ID NO: 276, 306, 300 and / or 330, and / or SEQ ID NO: 276, 306, 289 and / or 319, and / or SEQ ID NO: 277, 307, 283 and / or 313, and / or SEQ ID NO: 277, 307, 290 and / or 320, and / or or SEQ ID NO: 282, 312, 297 and / or 327, or any other combination of these sequences described herein that are within 50-60 amino acids of each other in one or more of the antigens of SEQ ID NO: 143- 158 and from 347 to 351; and / or SEQ ID NO: 18, 19 and / or 20 and / or SEQ ID NO: 34-40; and / or SEQ ID NO corresponding to the peptides shown in table 17, 20 and / or 23 that have a value of N%*B% less than 12%, 13%, 14%, 17.6 %, 17.8%, 18%, 20%, 21%, 22%, 22.2%, 24%, 25%, 27%, 28%, 30%, 31%, 31.5%, 32%, 32.5% or 35%. In some cases, the peptide panel comprises or consists of one or more polypeptides comprising or consisting of the amino acid sequences of SEQ ID NO: 130, 121, 131, 124, 134, 126 and / or SEQ ID NO: 435- 449.; In some cases, the description provides a panel of two or more of the peptides or groups of peptides described above. For example, the panel may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 5, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more of said peptides. In some cases, the panel comprises or consists of peptides comprising or consisting of all or any combination of the amino acid sequences of SEQ ID NO: 99, 100, 92, 93, 101, 103, 104, 105 and 98; or the amino acid sequences of SEQ ID NO: 121, 124, 126, 127, 130, 131, 132, 133 and 134. In some cases, the panel comprises or consists of peptides that comprise or consist of all or any combination of the amino acid sequences of SEQ ID NO: SEQ ID NO: 130, 121, 131, 124, 134, 126 and / or SEQ ID NO: 435-449. Pharmaceutical compositions, methods of treatment and modes of administration In some aspects, the description refers to a pharmaceutical composition, kit or panels of polypeptides as described above having one or more polypeptides as active ingredients. These may be for use in a method of inducing an immune response, treating, vaccinating, or providing immunotherapy to a subject, and the pharmaceutical composition may be a vaccine or immunotherapy composition. Said treatment comprises administering one or more polypeptides or pharmaceutical compositions that together comprise all the polypeptides of the active ingredient of the treatment to the subject. Multiple polypeptides or pharmaceutical compositions can be administered together or sequentially, for example, all of the pharmaceutical compositions or polypeptides can be administered to the subject within a period of 1 year, 6 months, 3 months or 60, 50, 40 or 30 days. The term "active ingredient", as used herein, refers to a polypeptide that is intended to induce an immune response and may include a polypeptide product of a vaccine or immunotherapy composition produced in vivo after administration to a subject. . For a DNA or RNA immunotherapy composition, the polypeptide may be produced in vivo by the cells of a subject to which the composition is administered. For a cell-based composition, the polypeptide may be processed and / or presented by cells of the composition, eg, autologous dendritic cells or antigen presenting cells pulsed with the polypeptide or comprising an expression construct encoding the polypeptide. The pharmaceutical composition may comprise a polynucleotide or a cell encoding one or more polypeptides of the active ingredient. The composition / kit may optionally further comprise at least one pharmaceutically acceptable diluent, carrier or preservative and / or additional polypeptides that do not comprise any PEPI. The polypeptides may be of non-natural origin or genetically modified. The kit may comprise one or more separate containers, each containing one or more of the active ingredient peptides. The composition / kit may be a personalized medicament to prevent, diagnose, alleviate, treat or cure an individual's disease, such as cancer. The immunogenic or pharmaceutical compositions or kits described herein may comprise, in addition to one or more immunogenic peptides, a pharmaceutically acceptable excipient, carrier, diluent, buffer, stabilizer, preservative, adjuvant, or other materials known to those of skill in the art. Said materials are preferably non-toxic and preferably do not interfere with the pharmaceutical activity of the active ingredients. The pharmaceutical carrier or diluent can be, for example, solutions containing water. The exact nature of the carrier or other material may depend on the route of administration, e.g. g., orally, intravenously, cutaneously or subcutaneously, nasally, intramuscularly, intradermally, and intraperitoneally. The pharmaceutical compositions of the disclosure may comprise one or more "pharmaceutically acceptable carriers". These are usually large slowly metabolized macromolecules, such as proteins, saccharides, polylactic acids, polyglycolic acids, polymeric amino acids, amino acid copolymers, sucrose (Paoletti et al., 2001, Vaccine, 19:2118), trehalose (WO 00 / 56365) , lactose and lipid aggregates (such as oil droplets or liposomes). Such carriers are known to those skilled in the art. Pharmaceutical compositions may also contain diluents, such as water, saline, glycerol, etc. Additionally, there may be auxiliary substances present, such as wetting or emulsifying agents, pH buffering substances, and the like. Sterile pyrogen-free phosphate-buffered physiological saline is a typical carrier (Gennaro, 2000, Remington: The Science and Practice of Pharmacy, 20th edition, ISBN:0683306472). The pharmaceutical compositions of the disclosure may be in lyophilized or aqueous form, ie, solutions or suspensions. Liquid formulations of this type allow the compositions to be administered directly from their packaged form, without the need for reconstitution in an aqueous medium, and thus are ideal for injection. The pharmaceutical compositions may be presented in vials or may be presented in pre-filled syringes. Syringes may or may not have needles. A syringe will include a single dose, while a vial may include a single dose or multiple doses. The liquid formulations of the disclosure are also suitable for the reconstitution of other medicaments from a lyophilized form. When a pharmaceutical composition is used for such extemporaneous reconstitution, the description provides a kit, which may comprise two vials, or may comprise a pre-filled syringe and a vial, where the contents of the syringe are used to reconstitute the contents of the vial prior to injection. injection. The pharmaceutical compositions of the disclosure may include an antimicrobial agent, particularly when packaged in a multi-dose format. Antimicrobial agents such as 2-phenoxyethanol or parabens (methyl, ethyl, propyl parabens) can be used. Any preservative is preferably present at low levels. The preservative may be added exogenously and / or may be a component of the bulk antigens that are mixed to form the composition (eg, present as a preservative in pertussis antigens). The pharmaceutical compositions of the disclosure may comprise detergent, e.g. g., Tween (polysorbate), DMSO (dimethylsulfoxide), DMF (dimethylformamide). Detergents are generally present at low levels, e.g. <0.01%, but can also be used at higher levels, eg 0.01-50%. The pharmaceutical compositions of the disclosure may include sodium salts (eg, sodium chloride) and free phosphate ions in solution (eg, by use of a phosphate buffer). In certain embodiments, the pharmaceutical composition may be encapsulated in a suitable carrier to deliver the peptides to antigen-presenting cells or to increase stability. As the skilled artisan will appreciate, various vehicles are suitable for delivering a pharmaceutical composition of the disclosure. Non-limiting examples of suitable structured fluid delivery systems may include nanoparticles, liposomes, microemulsions, micelles, dendrimers, and other phospholipid-containing systems. Methods for incorporating pharmaceutical compositions into delivery vehicles are known in the art. To increase the immunogenicity of the composition, the pharmacological compositions may comprise one or more adjuvants and / or cytokines. Suitable adjuvants include an aluminum salt, such as aluminum hydroxide or aluminum phosphate, but may also be a calcium, iron, or zinc salt, may be an insoluble suspension of acylated tyrosine or acylated sugars, or may be cationic derived saccharides. or Anionically, Polyphosphazenes, Biodegradable Microspheres, Monophosphorylated Lipid A (MPL), Lipid A Derivatives (eg, Reduced Toxicity), 3-O-Deacetylated MPL [3D-MPL], Quil A, Saponin, QS21, Adjuvant incomplete from Frcund (Difeo Laboratories, Detroit, Mich.), adjuvant 65 from Merck (Merck and Company, Inc., Rahway, N.J.), AS-2 (Smith-Kline Beecham, Philadelphia, Pa.), CpG oligonucleotides, bioadhesives and mucoadhesives, microparticles, liposomes, polyoxyethylene ether formulations, polyoxyethylene ester formulations, muramyl peptides, or imidazoquinolone compounds (eg, imiquamod and its homologues). Human immunomodulators suitable for use as adjuvants in the disclosure include cytokines, such as interleukins (eg, IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL- 12, etc.), macrophage colony-stimulating factor (M-CSF), tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) can also be used as adjuvants . In some embodiments, the compositions comprise an adjuvant selected from the group consisting of Montanide ISA-51 (Seppic, Inc., Fairfield, N.J., United States of America), QS-21 (Aquila Biopharmaceuticals, Inc., Lexington, Mass., United States of America), GM-CSF, Cyclophosamide, Bacillus Calmette-Guerin (BCG), Corynbacterium Parvum, Levamisole, Azimezone, Isoprinisone, Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (complete and incomplete ), mineral gels, aluminum hydroxide (Alum), lysolecithin, pluronic polyols, polyanions, oil emulsions, dinitrophenol, diphtheria toxin (DT). By way of example, the cytokine may be selected from the group consisting of transforming growth factor (TGF) such as, but not limited to, TGF-α and TGF-β; insulin-like growth factor type I and / or insulin-like growth factor type II; erythropoietin (EPO); an osteoinductive factor; an interferon such as, but not limited to, interferon-.α, -β, and -γ; a colony-stimulating factor (CSF) such as, but not limited to, macrophage-CSF (M-CSF); granulocyte-macrophage-CSF (GM-CSF); and granulocyte-CSF (G-CSF). In some embodiments, the cytokine is selected from the group consisting of nerve growth factors such as NGF-β; platelet growth factor; a transforming growth factor (TGF) such as, but not limited to, TGF-α. and TGF-β, insulin-like growth factor type I and insulin-like growth factor type II; erythropoietin (EPO); an osteoinductive factor; an interferon (IFN) such as, but not limited to, IFN-a, IFN-β, and IFN-γ; a colony stimulating factor (CSF) such as macrophage-CSF (M-CSF); granulocyte-macrophage-CSF (GM-CSF); and granulocyte-CSF (G-CSF); an interleukin (II) such as, but not limited to, IL-1, IL-l.alpha., IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL -9, IL-10, IL-11, IL-12; IL-13. IL-14, IL-15, IL-16, IL-17, IL-18; LIF; kit-ligand or FLT-3; angiostatin; thrombospondin; endostatin; a tumor necrosis factor (TNF); and LT. It is expected that an adjuvant or cytokine may be added in an amount of from about 0.01 mg to about 10 mg per dose, preferably in an amount of from about 0.2 mg to about 5 mg per dose. Alternatively, the adjuvant or cytokine may be in a concentration of between about 0.01 and 50%, preferably in a concentration of between about 2% and 30%. In certain aspects, the pharmaceutical compositions of the disclosure are prepared by physically mixing the adjuvant and / or cytokine with the peptides of the disclosure under suitable sterile conditions in accordance with known techniques to produce the final product. Examples of suitable compositions of the invented polypeptide fragments and methods of administration are provided in Esseku and Adeyeye (2011) and Van den Mooter G. (2006). The preparation of vaccine and immunotherapy compositions is generally described in Vaccine Design ("The subunit and adjuvant approach" (ed. Powell M. F. & Newman M. J. (1995) Plenum Press, New York). Encapsulation within liposomes, which is also contemplates, is described by Fullerton, US Patent 4,235,877. In some embodiments, the compositions described herein are prepared as a nucleic acid vaccine. In some embodiments, the nucleic acid vaccine is a DNA vaccine. In some embodiments, DNA vaccines, or gene vaccines, comprise a plasmid with a suitable promoter and transcriptional and translational control elements and a nucleic acid sequence encoding one or more polypeptides of the invention. In some embodiments, plasmids also include sequences to enhance, for example, expression levels, intracellular targeting, or proteasome processing. In some embodiments, DNA vaccines comprise a viral vector containing a nucleic acid sequence encoding one or more polypeptides of the disclosure. In additional aspects, the compositions described herein comprise one or more peptide-encoding nucleic acids determined to have immunoreactivity with a biological sample. For example, in some embodiments, compositions comprise one or more nucleotide sequences encoding 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more peptides comprising a fragment that is a T cell epitope capable of binding to at least three HLA class I molecules and / or at least three HLA class II molecules from a patient. In some embodiments, the peptides are derived from an antigen expressed in cancer. In some embodiments, the DNA or gene vaccine also encodes immunomodulatory molecules to manipulate the resulting immune responses, eg, to increase the potency of the vaccine, stimulate the immune system, or reduce immunosuppression. Strategies to increase the immunogenicity of DNA or gene vaccines include encoding xenogeneic versions of antigens, fusion of antigens to molecules that activate T cells or activate associative recognition, DNA vector priming followed by viral vector boosting and the use of immunomodulatory molecules. In some embodiments, the DNA vaccine is delivered by needle, gene gun, aerosol injector, patch, microneedle, abrasion, among other ways. In some forms, the DNA vaccine is incorporated into liposomes or other forms of nanobodies. In some embodiments, the DNA vaccine includes a delivery system selected from the group consisting of a transfection agent; protamine; a protamine liposome; a polysaccharide particle; a cationic nanoemulsion; a cationic polymer; a cationic polymer liposome; a cationic nanoparticle; a cationic lipid and cholesterol nanoparticle; a cationic lipid, cholesterol and PEG nanoparticle; a dendrimer nanoparticle. In some embodiments, DNA vaccines are administered by inhalation or ingestion. In some embodiments, the DNA vaccine is introduced into the blood, thymus, pancreas, skin, muscle, tumor, or other sites. In some embodiments, the compositions described herein are prepared as an RNA vaccine. In some embodiments, the RNA is non-replicating mRNA or virally derived self-amplifying RNA. In some embodiments, the non-replicating mRNA encodes the peptides described herein and contains the 5' and 3' untranslated regions (UTRs). In some embodiments, the virally derived self-amplifying RNA encodes not only the peptides described herein but also the viral replication machinery that enables intracellular RNA amplification and abundant protein expression. In some embodiments, the RNA is introduced directly into the individual. In some embodiments, the RNA is chemically synthesized or transcribed in vitro. In some embodiments, mRNA is produced from a linear DNA template using an RNA polymerase from phage T7, T3, or Spó, and the resulting product contains an open reading frame encoding the peptides described herein, flanking UTRs, a 5' cap and a poly(A) tail. In some embodiments, various versions of 5' caps are added during or after the transcription reaction using a vaccinia virus capping enzyme or by incorporation of synthetic cap or anti-reverse cap analogs. In some embodiments, an optimal length of poly(A) tail is added to the mRNA, either directly from the encoding DNA template or through the use of poly(A) polymerase. The RNA encodes one or more peptides comprising a fragment that is a T cell epitope capable of binding to at least three HLA class I molecules and / or at least three HLA class II molecules from a patient. In some embodiments, the fragments are derived from an antigen expressed in cancer. In some embodiments, the RNA includes signals to enhance stability and translation. In some embodiments, the RNA also includes unnatural nucleotides to increase half-life or modified nucleosides to change the immunostimulatory profile. In some embodiments, RNAs are delivered by needle, gene gun, aerosol injector, patching, microneedling, abrasion, among other ways. In some forms, the RNA vaccine is incorporated into liposomes or other forms of nanobodies that facilitate cellular uptake of the RNA and protect it from degradation. In some embodiments, the RNA vaccine includes a delivery system selected from the group consisting of a transfection agent; protamine; a protamine liposome; a polysaccharide particle; a cationic nanoemulsion; a cationic polymer; a cationic polymer liposome; a cationic nanoparticle; a cationic lipid and cholesterol nanoparticle; a cationic lipid, cholesterol and PEG nanoparticle; a dendrimer nanoparticle; and / or naked mRNA; Naked mRNA electroporated in vivo; mRNA complexed with protamine; mRNA associated with a positively charged cationic oil-in-water nanoemulsion; mRNA associated with a chemically modified dendrimer and complexed with polyethylene glycol (PEG)-lipid; mRNA that complexes with protamine on a PEG-lipid nanoparticle; mRNA associated with a cationic polymer such as polyethyleneimine (PEI); mRNA associated with a cationic polymer such as PEI and a lipid component; mRNA associated with a polysaccharide (eg chitosan), particle or gel; mRNA in a cationic lipid nanoparticle (eg, 1,2-dioleoyloxy-3-trimethylammoniompropane (DOTAP) or dioleoylphosphatidylethanolamine (DOPE) lipids); mRNA that forms complexes with cationic lipids and cholesterol; or mRNA that forms complexes with cationic lipids, cholesterol, and PEG-lipid. In some embodiments, the RNA vaccine is administered by inhalation or ingestion. In some embodiments, the RNA is introduced into blood, thymus, pancreas, skin, muscle, tumor, or other sites, and / or by intradermal, intramuscular, subcutaneous, intranasal, intranodal, intravenous, intrasplenic, intratumoral or other route of administration. The polynucleotide or oligonucleotide components may be naked nucleotide sequences or in combination with cationic lipids, polymers, or targeting systems. They can be supplied through any available technique. For example, the polynucleotide or oligonucleotide can be introduced by needle injection, preferably intradermally, subcutaneously, or intramuscularly. Alternatively, the polynucleotide or oligonucleotide can be delivered directly through the skin using a delivery device such as particle-mediated gene delivery. The polynucleotide or oligonucleotide can be administered topically to skin or mucosal surfaces, for example, by intranasal, oral, or intrarectal administration. Uptake of polynucleotide or oligonucleotide constructs can be enhanced through various known transfection techniques, for example, including the use of transfection agents. Examples of these agents include cationic agents, eg, calcium phosphate and DEAE-Dextran, and lipofectants, eg, lipofectam and transfectam. The dosage of the polynucleotide or oligonucleotide to be administered can be altered. Administration is typically a "prophylactically effective amount" or a "therapeutically effective amount" (as the case may be, although prophylaxis may be considered therapy), where this is sufficient to elicit a clinical response or to show clinical benefit to the individual, p. eg, an amount effective to prevent or delay the onset of the disease or condition, to ameliorate one or more symptoms, to induce or prolong remission, or to delay relapse or recurrence. The dose can be determined according to various parameters, especially according to the substance used; the age, weight and condition of the individual treated; the route of administration; and the necessary regimen. The amount of antigen in each dose is selected as an amount that induces an immune response. A physician will be able to determine the route of administration and dosage necessary for any particular individual. The dose may be provided as a single dose or may be provided as multiple doses, eg, taken at regular intervals, eg, 2, 3, or 4 doses administered hourly. Typically, peptides, polynucleotides, or oligonucleotides are typically administered in the range of 1 pg to 1 mg, more typically 1 pg to 10 pg for particle-mediated delivery and 1 pg to 1 mg, more typically 1-100 pg. , more typically 5-50 pg for other pathways. In general, each dose is expected to comprise 0.01-3 mg of antigen. An optimal amount for a particular vaccine can be determined through studies involving observation of immune responses in subjects. Examples of the aforementioned techniques and protocols can be found in Remington's Pharmaceutical Sciences, 20th edition, 2000, pub. Lippincott, Williams & Wilkins. In some cases according to the description, more than one peptide or peptide composition is administered. Two or more pharmaceutical compositions can be administered together / dc simultaneously and / or at different times or sequentially. Thus, the description includes sets of pharmaceutical compositions and uses thereof. The use of a combination of different peptides, optionally directed to different antigens, is important to overcome the challenge of the genetic heterogeneity of tumors and the HLA heterogeneity of individuals. The use of the peptides of the disclosure in combination expands the group of individuals who may experience clinical benefit from vaccination. Multiple pharmaceutical compositions of the peptides of the disclosure, manufactured for use in a regimen, can define a drug product. Routes of administration include, but are not limited to, intranasal, oral, subcutaneous, intradermal, and intramuscular. Subcutaneous administration is particularly preferred. Subcutaneous administration, for example, may be by injection into the abdomen, the lateral and anterior portions of the upper arm or thigh, the scapular area of ​​the back, or the upper ventrodorsal gluteal area. The compositions of the disclosure can also be administered in one or more doses, as well as by other routes of administration. For example, such routes include, intracutaneous, intravenous, intravascular, intraarterial, intraperitoneal, intrathecal, intratracheal, intracardiac, intralobular, intramedullary, intrapulmonary, and intravaginal routes. Depending on the desired duration of treatment, the compositions according to the description can be administered once or several times, also intermittently, for example monthly for several months or years and in different dosages. Solid dosage forms for oral administration include capsules, tablets, pills, pills, powders, tablets, and granules. In such solid dosage forms, the active ingredient is commonly combined with one or more pharmaceutically acceptable excipients, examples of which are detailed above. Oral preparations such as aqueous suspensions, elixirs, or syrups may also be administered. For these, the active ingredient can be combined with various sweetening or flavoring agents, coloring agents and, if desired, emulsifying and / or suspending agents, as well as diluents such as water, ethanol, glycerin and combinations of these. One or more compositions of the description can be administered, or the methods and uses for treatment according to the description can be performed, alone or in combination with other compositions or pharmacological treatments, for example, chemotherapy, immunotherapy and / or vaccine. The other compositions or therapeutic treatments, for example, may be one or more of those set forth herein, and may be administered simultaneously or sequentially (before or after) with the composition or treatment of the disclosure. In some cases, treatment may be given in combination with checkpoint blockade therapy, costimulatory antibodies, chemotherapy and / or radiation therapy, targeted therapy, or monoclonal antibody therapy. Chemotherapy has been shown to sensitize tumors to be killed by vaccination-induced tumor-specific cytotoxic T cells (Ramakrishnan et al. J Clin Invest. 2010;120(4):1111-1124). Examples for checkpoint inhibitors are CTLA-4 inhibitor, Ipilimumab and Programmed Cell Death-1 / Programmed Cell Death Ligand-1 (PD-1 / PD-L1) signaling inhibitors, Nibolumab, Pembrolizumab, Atezolizumab, and Durvalumab . Examples of chemotherapy agents include alkylating agents including nitrogen mustards such as mechlorethamine (HN2), cyclophosphamide, ifosfamide, melphalan (L-sarcolysin), and chlorambucil; anthracyclines; epothilones; nitrosoureas such as carmustine (BCNU), lomustine (CCNU), semustine (methyl-CCNU), and streptozocin (streptozotocin); triazenes such as decarbazine (DTIC; dimethyltriazenoimidazole-carboxamide; ethylenimines / methylmelamines such as hexamethylmelamine, thiotepa; alkyl sulfonates such as busulfan; antimetabolites including folic acid analogs such as methotrexate (ametopterin); alkylating agents, antimetabolites, pyrimidine analogs such as such as fluorouracil (5-fluorouracil; 5-FU), floxuridine (fluorodeoxyuridine; FUdR), and cytarabine (cytosine arabinoside); purine analogs and related inhibitors such as mercaptopurine (6-mercaptopurine; 6-MP), thioguanine (6-thioguanine ; TG) and pentostatin (2'-deoxycoformycin); epipodophyllotoxins; enzymes such as L-asparaginase; biological response modifiers such as IFNa, IL-2, G-CSF and GM-CSF; platinum coordination complexes such as cisplatin ( cis-DDP), oxaliplatin and carboplatin; anthracendones such as mitoxantrone and anthracycline; substituted urea such as hydroxyurea; methylhydrazine derivatives including procarba zine (N-methylhydrazine, MIH) and procarbazine; adrenocortical suppressants such as mitotane (o,p'-DDD) and aminoglutethimide; taxol and analogs / derivatives; hormones and agonists / antagonists including adrenocorticosteroid antagonists such as prednisone and equivalents, dexamethasone and aminoglutethimide, progestins such as hydroxyprogesterone caproate, medroxyprogesterone acetate and megestrol acetate, estrogens such as diethylstilbestrol and ethinylestradiol equivalents, antiestrogens such as tamoxifen, androgens including testosterone propionate and fluoxymesterone / equivalents, antiandrogens such as flutamide, gonadotropin-releasing hormone analogs, and leuprolide and nonsteroidal antiandrogens such as flutamide; natural products including vinca alkaloids such as vinblastine (VLB) and vincristine, epipodophyllotoxins such as etoposide and teniposide, antibiotics such as dactinomycin (actinomycin D), daunorubicin (daunomycin; rubidomycin), doxorubicin, bleomycin, plicamycin (mithramycin), and mitomycin (mitomycin C), enzymes such as L-asparaginase, and biological response modifiers such as interferon alphenomes. In some cases, the method of treatment is a method of vaccination or a method of providing immunotherapy. As used herein, "immune" is the prevention or treatment of a disease or condition by inducing or enhancing an immune response in an individual. In certain embodiments, immunotherapy refers to a therapy comprising the administration of one or more drugs to an individual to elicit T cell responses. In a specific embodiment, immunotherapy refers to a therapy comprising the administration or expression of polypeptides containing one or more PEPIs to an individual to elicit a T cell response to recognize and kill cells that display the PEPI(s) on their cell surface along with HLA class I. In another specific embodiment, immunotherapy comprises the administration of one or more PEPI to an individual to elicit a cytotoxic T-lymphocyte response against cells that present tumor-associated antigens (TAA) or cancer-associated antigens (CTA) that comprise the PEPI(s) on their cell surface. In another embodiment, immunotherapy refers to a therapy comprising the administration or expression of polypeptides containing one or more PEPIs presented by HLA class II to an individual to elicit a helper T cell response to provide costimulation for cytotoxic T cells that recognize and destroy diseased cells that present the PEPI(s) on their cell surface along with an HLA class I. In yet another specific embodiment, immunotherapy refers to a therapy comprising the administration of one or more drugs to an individual that reactivate lymphocytes existing T cells to destroy target cells. The theory is that the cytotoxic T cell response will eliminate the cells presenting the PEPI(s), thus improving the individual's clinical condition. In some cases, immunotherapy can be used to treat tumors. In other cases, immunotherapy can be used to treat diseases or disorders based on intracellular pathogens. In some cases, the description refers to the treatment of cancer or the treatment of solid tumors. In some cases, the treatment is for breast cancer, ovarian cancer, or colorectal cancer. In other cases, the treatment may be of any other cancer or solid tumor that expresses a tumor associated antigen target of the present peptides as described herein, or any cancer in which said target polypeptide antigens are expressed in some or a high percentage of subjects. The treatment can be of malignant or benign cancers or tumors of any type of cell, tissue or organ. The cancer may or may not be metastatic. Exemplary cancers include carcinomas, sarcomas, lymphomas, leukemias, germ cell tumors, or blastemas. The cancer may or may not be a hormone-dependent or hormone-related cancer (eg, an estrogen- or androgen-related cancer). Selection of polypeptides and patients Specific polypeptide antigens, and particularly short antigens derived from such antigens, which are commonly used in vaccination and immunotherapy, induce immune responses in only a fraction of human subjects. The polypeptides of the present disclosure are specifically selected to induce immune responses in a high proportion of the general population, but may not be effective in all individuals due to heterogeneity of HLA genotype. Population heterogeneity of HLA genotype means that the rate of clinical or immune response to the vaccines described herein differ between different human subpopulations. In some cases, the vaccines described herein are for use to treat a specific or targeted subpopulation, eg, an Asian population or a Vietnamese, Chinese, and / or Japanese population. The disclosure also provides a method for identifying a human subject likely to have a cytotoxic T-lymphocyte response to the administration of a pharmaceutical composition comprising a peptide of the disclosure (potential responders), or for predicting the likelihood that a subject will have a cytotoxic T-lymphocyte response. cytotoxic T lymphocyte response. As provided herein, presentation of T-cell epitopes by multiple HLAs from an individual is generally needed to activate a T-cell response. The best predictor of a cytotoxic T-cell response to a given polypeptide, as determined by the inventors, is the presence of at least one T cell epitope presented by three or more HLA class I of an individual (<1 PEPI3+). Accordingly, the presence within the active ingredient peptides of a pharmaceutical composition of one or more T-cell epitopes that is capable of binding to at least three HLAs from a subject predicts that the subject has a cytotoxic T-cell response to cytotoxic T-cell infection. administration of the pharmaceutical composition. Subject is a possible immune responder. In some cases, the T cell epitope that is capable of binding to at least three class I HLAs of the subject has the amino acid sequence of either SEQ ID NO: 1 to 40 or SEQ ID NO: 1 to 40, 172-194, 234-250 and 272-301. In other cases, the T cell epitope may have a different amino acid sequence within one or more peptides of the pharmaceutical composition. The inventors further discovered that the presence in an immunotherapy or vaccine composition of at least two epitopes that can bind to at least three HLAs of an individual predicts a clinical response. In other words, if an individual has a total of <2 PEPI3+ within the active ingredient polypeptides of an immunotherapy or vaccine composition, and these PEPI3+ are derived from antigen sequences that are in fact expressed in the individual (for example, the target tumor cells of the individual express the target tumor-associated antigens), the individual is a potential clinical responder (ie, a clinically relevant immune responder). Accordingly, some aspects of the disclosure relate to a method of identifying a subject likely to have a clinical response to a method of treatment in accordance with the disclosure, or of predicting the likelihood that a subject will have a clinical response. A "clinical response" or "clinical benefit", as used herein, may be the prevention or delay in onset of a disease or condition, the improvement of one or more symptoms, the induction or prolongation of remission, or the delay of a relapse, recurrence or deterioration, or any other improvement or stabilization of a subject's disease state. Where appropriate, a "clinical response" may correlate with "disease control" or an "objective response" as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. In some embodiments, the method comprises determining that one or more cancer-associated antigens selected from SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-All, PRAME, MAGE-A9, HOM-TES-85, TSP50, EpCAM, CAGE1, FBXO39, MAGE-A8 and MAGE-A6 are expressed by cancer. For example, cancer-associated antigen expression can be detected in a sample obtained from the subject, eg, a tumor biopsy, using methods that are known in the art. The inventors discovered that it is not enough for a vaccine or immunotherapy composition to target an antigen expressed by a patient's cancer or tumor cells, nor to target sequences of that antigen that can bind to the patient's HLA class I (epitopes HLA-restricted). The composition is likely to be effective only in patients who express the target antigen and who have three or more HLA class I that bind to a single T cell epitope of the target antigen. Furthermore, as described above, at least two epitopes that bind to at least 3 HLAs in the patient are generally required to induce a clinically relevant immune response. Therefore, the method further comprises determining that the peptides of the active ingredient of the pharmaceutical composition comprise two or more different amino acid sequences, each of which is a) a fragment of a cancer-associated antigen expressed by cancer cells of the subject , as determined as described above; and b) a T cell epitope capable of binding to at least three HLA class I of the subject. In some cases, the T cell epitope that is capable of binding to at least three class I HLAs of the subject has the amino acid sequence of either SEQ ID NO: 1 to 40 or SEQ ID NO: 1 to 40, 172-194, 234-250 and 272-301. In other cases, the T cell epitope may have a different amino acid sequence within one or more peptides of the pharmaceutical composition. In some cases, the likelihood that a subject will have a clinical response to a peptide vaccine or immunotherapy composition, such as those described herein, can be determined without knowing whether the target antigens are expressed on cancer or tumor cells of the subject. and / or without determining the HLA class I genotype of the subject. Known frequencies of antigen expression in the disease (eg, MAGE-A3 in a tumor type such as breast or colorectal cancer) and / or known frequencies for HLA class I genotype can be used instead and class II of subjects in the target population (eg, ethnic population, general population, diseased population).Furthermore, by combining peptides that target PEPIs that occur most frequently throughout the population (BestEPIs) across multiple target antigens frequently expressed in disease, as identified and described herein, it is possible to design a regimen effective cancer vaccine for a high proportion of patients. However, use of the companion diagnostic methods described herein to preselect patients who are more likely to have a clinical response will increase clinical response rates among treated patients. The probability that a subject will respond to treatment is increased by (i) the presence of more multi-HLA binding PEPI in the active ingredient polypeptides; (ii) the presence of PEPI on more target polypeptide antigens; and (iii) expression of the target polypeptide antigens in the subject or in diseased cells of the subject. In some cases, the expression of the target polypeptide antigens in the subject may be known, for example, if there are target polypeptide antigens in a sample obtained from the subject. In other cases, the probability that a specific subject, or diseased cells from a specific subject, will (over)express a specific target polypeptide antigen or any combination of target polypeptide antigens can be determined using population expression frequency data, p . eg, the probability of expression of an antigen in breast cancer, colorectal cancer or ovarian cancer. The population expression frequency data may refer to a population corresponding to the subject and / or the disease or the intention-to-treat population. For example, the frequency or probability of expression of a particular cancer-associated antigen in a particular cancer or subject having a particular cancer, eg, breast cancer, can be determined by detecting the antigen in the tumor, eg, breast cancer. eg, breast cancer tumor samples. In some cases, such expression frequencies can be determined from scientific publications and published figures. In some cases, a method of the disclosure comprises a step of determining the frequency of expression of a relevant target polypeptide antigen in a relevant population. A series of pharmacodynamic biomarkers for predicting the activity / effect of vaccines in individual human subjects as well as in populations of human subjects are described. These biomarkers facilitate more efficient vaccine development and also lower the cost of development, and can be used to evaluate and compare different compositions. The following are exemplary biomarkers. • AG95 - potency of a vaccine: the amount of antigens in a cancer vaccine that a specific tumor type expresses with a 95% probability. AG95 is an indicator of vaccine potency and is independent of the immunogenicity of the vaccine antigens. AG95 is calculated from tumor antigen expression rate data. Such data can be obtained from experiments published in peer-reviewed scientific journals. Technically, AG95 is determined from the binomial distribution of antigens in the vaccine, and considers all possible variations and expression rates.• PEPI3+ count - immunogenicity of a vaccine in a subject: vaccine-derived PEPI3+ are personal epitopes that are they bind to at least 3 HLAs in a subject and induce T cell responses. PEPI3+ can be determined using the PEPI3+ test in subjects whose full 4-digit HLA genotype is known.• AP count - antigenicity of a vaccine in one subject: quantity of PEPI3+ vaccine antigens. Vaccines contain target polypeptide antigen sequences expressed by diseased cells. The PA count is the number of antigens in the vaccine that contain PEPI3+, and the PA count represents the number of antigens in the vaccine that can induce T cell responses in a subject. The AP count characterizes the subject's vaccine antigen-specific T cell responses as it depends only on the subject's HLA genotype and is independent of the subject's disease, age, and medication. The correct value is between 0 (no PEPI presented by the antigen) and the maximum number of antigens (all antigens present PEPI).• AP50 - antigenicity of a vaccine in a population: The average amount of vaccine antigens with a PEPI in a population. The AP50 is suitable for the characterization of vaccine antigen-specific T cell responses in a given population as it is dependent on the HLA genotype of subjects in a population.• AGP count - efficacy of a vaccine in a subject: amount of tumor-expressed vaccine antigens with PEPI. The AGP count indicates the amount of tumor antigens that the vaccine recognizes and induces a T-lymphocyte response against them (achieves the target). The AGP count depends on the rate of expression of the vaccinia antigen in the subject's tumor and the subject's HLA genotype. The correct value is between 0 (no PEPI presented by the expressed antigen) and the maximum number of antigens (all antigens are expressed and present a PEPI).• AGP50 - efficacy of a cancer vaccine in a population: the amount Mean number of vaccine antigens expressed in PEPI-indicated tumor (ie, AGP) in a population. The AGP50 indicates the mean amount of tumor antigens that can be recognized by vaccine-induced T cell responses. AGP50 depends on the expression rate of the antigens in the indicated tumor type and the immunogenicity of the antigens in the target population. AGP50 can estimate vaccine efficacy in different populations and can be used to compare different vaccines in the same population. The calculation of AGP50 is similar to that used for AG50, except that expression is weighted by the occurrence of PEPI3+ in the subject at expressed vaccine antigens. In a theoretical population, where each subject has a PEPI of each vaccine antigen, the AGP50 will be equal to AG50. In another theoretical population, where no subject has a PEPI of any vaccine antigen, the AGP50 will be 0. In general, the following statement is valid: 0 > AGP50 > AG50.• mAGP - a candidate biomarker for the selection of potential responders: probability that a cancer vaccine will induce T cell responses against multiple antigens expressed in the indicated tumor. mAGP is calculated from the expression rates of vaccinia antigens in the tumor and the presence of vaccinia-derived PEPI in the subject. Technically, based on the AGP distribution, the mAGP is the sum of the probabilities of the multiple AGPs (<2 AGPs). The results of a prediction as stated above can be used to inform a physician's decisions regarding treatment of the subject. Accordingly, in some cases the method of the disclosure predicts that a subject will have or is likely to have a T cell response and / or a clinical response to a treatment as described herein, and the method further comprises selecting the treatment for the human subject. In some cases, a subject is selected for treatment if his or her probability of a response directed at a predefined number of target polypeptide antigens, optionally where target polypeptide antigens are (predicted) to be expressed, is greater than a predetermined threshold. . In some cases, the number of target polypeptide epitopes or antigens is two. In some cases, the number of target polypeptide epitopes or antigens is three, four, five, six, seven, eight, nine or ten. The method may further comprise administering the treatment to the human subject. Alternatively, the method may predict that the subject will not have an immune response and / or a clinical response and further comprise selecting a different treatment for the subject. Additional modalities of the description - (1) 1. A pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any of SEQ ID NO: from 112 to 142.2. The pharmaceutical composition of item 1 comprising 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides or 6 or more peptides.3. The pharmaceutical composition of item 1 comprising two peptides, where each peptide comprises a different sequence of the amino acid sequences of SEQ TD NO: 121 and 124.4. The pharmaceutical composition of item 1 comprising four peptides, where each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 126, 130, 131 and 134.5. The pharmaceutical composition of item 1 comprising six peptides, where each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 121, 124, 126, 130, 131 and 134.6. The pharmaceutical composition of item 5 further comprising at least one additional peptide comprising a fragment of an antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8 and MAGE-A6.7. The pharmaceutical composition of item 5 that further comprises one or more additional peptides, where each of these additional peptides comprises a sequence different from the amino acid sequence of any of SEQ ID NO: 112-120, 122, 123, 125, 127- 129, 132, 133 and 135-142. 8. The pharmaceutical composition of item 1 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.9. The pharmaceutical composition of item 8, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone , Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, diphtheria toxin (DT) and combinations of these.10. A pharmaceutical composition comprising one or more nucleic acid molecules encoding one or more peptides, wherein each peptide comprises a sequence other than the amino acid sequence of any of SEQ ID NO: 112 to 142.11.A method of identifying and treating a human subject suffering from a cancer that is likely to have a clinical response to the administration of a pharmaceutical composition according to item 1, wherein the method comprises (i) assaying a biological sample of the subject for determining the HLA genotype of the subject; (ii) determining that the pharmaceutical composition comprises two or more sequences that are a T cell epitope capable of binding to at least three HLA class I molecules of the subject; (iii) determining the probability that a subject's tumor expresses one or more antigens corresponding to the T cell epitopes identified in step (ii) using the population expression data for each antigen, to identify the likelihood that the subject will have a clinical response to administering the pharmaceutical composition; and (iv) administering the composition of item 1 to the identified subject. 12. The method of item 11, where the subject has colorectal cancer.13. The method of item 11, where the pharmaceutical composition comprises 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, or 6 or more peptides.14. The method of item 11, wherein the pharmaceutical composition comprises two peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 121 and 124. 15. The method of item 11, wherein the pharmaceutical composition comprises four peptides, where each peptide comprises a different sequence from the amino acid sequences of SEQ ID NO: 126, 130, 131 and 134.16. The method of item 11, wherein the pharmaceutical composition comprises six peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 121, 124, 126, 130, 131 and 134.17. The method of item 11, wherein the pharmaceutical composition further comprises at least one additional peptide comprising a fragment of an antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8 and MAGE-A6.18. The method of item 11, wherein the pharmaceutical composition further comprises one or more additional peptides, where each of these additional peptides comprises a sequence different from the amino acid sequence of any of SEQ ID NO: 112-120, 122, 123, 125, 127-129, 132, 133 and 135-142.19. The method of item 11, where the pharmaceutical composition also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.20. The method of item 19, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone, Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, Toxin of diphtheria (DT) and combinations of these.21. The method of item 11 which further comprises administering a chemotherapeutic agent, a checkpoint inhibitor, a targeted therapy, radiation therapy, another immunotherapy or a combination of these to the identified subject.22. The method of item 13 further comprising, prior to the administration step, (i) performing an assay on a tumor sample from a subject to determine that the three or more peptides of the pharmaceutical composition comprise two or more different amino acid sequences, each of which is a. a fragment of a cancer-associated antigen expressed by cancer cells of the subject as determined in step (i); and b. a T cell epitope capable of binding to at least three HLA class I molecules from the subject; and (ii) confirm that the subject is likely to have a clinical response to the method of treatment. Additional modalities of the description - (2) Breast cancer 1. A pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a different sequence of the amino acid sequence of any of SEQ ID NO: from 81 to 111 and from 435 to 449.2. The pharmaceutical composition of item 1 comprising 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, more peptides or 12 or more peptides.3. The pharmaceutical composition of item 1 comprising 9 peptides, where each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 92, 93, 98, 99-101 and 103-105.4. The pharmaceutical composition of item 1 that further comprises at least one additional peptide comprising a fragment of an antigen selected from PIWIL-2, AKAP-4, EpCAM, BORIS, HIWI, SPAG9, PLU-1, TSGA10, ODF-4, SP17 , RHOXF-2, PRAME, NY-SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-A11, HOM-TES-85 and NY-ESO-1.5. The pharmaceutical composition of item 4, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ TD NO: from 1 to 20, 24 and from 172 to 194.6. The pharmaceutical composition of item 4, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ ID NO:41-60 and 195-233.7. The pharmaceutical composition of item 1 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.8. The pharmaceutical composition of item 7, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone , Dinitrochlorobenzene (DNCB), Keyhole Limpet Hcmocyanin (KLH), Frcund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, diphtheria toxin (DT) and combinations of these. 9. A pharmaceutical composition comprising one or more nucleic acid molecules encoding one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any of SEQ ID NO: de81allyde 435 to 449.10. The pharmaceutical composition of item 9, where the nucleic acid molecule(s) encode 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, or more peptides, or 12 or more peptides.11. The pharmaceutical composition of item 9, wherein the nucleic acid molecule(s) encode 9 peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 92, 93, 98, 99-101 and 103- 105.12. The pharmaceutical composition of item 9, wherein the nucleic acid molecule(s) encode at least one additional peptide comprising a fragment of an antigen selected from PIWIL-2, AKAP-4, EpCAM, BORIS, HIWI, SPAG9, PLU-1 , TSGA10, ODF-4, SP17, RHOXF-2, PRAME, NY-SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-A11, HOM-TES-85 and NY-ESO-1.13. The pharmaceutical composition of item 12, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ ID NO: from 1 to 20, 24 and from 172 to 194.14. The pharmaceutical composition of item 12, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ ID NO:41-60 and 195-233.15. The pharmaceutical composition of item 9 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.16. The pharmaceutical composition of item 15, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone , Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanionics, Oil Emulsions, Dinitrophnol, diphtheria toxin (DT) and combinations of these.17.A method of identifying and treating a human subject suffering from a cancer that is likely to have a clinical response to the administration of a pharmaceutical composition according to item 1, wherein the method comprises (i) assaying a biological sample of the subject for determine the HLA genotype of the subject; (ii) determine that the pharmaceutical composition comprises two or more sequences that are a T cell epitope capable of binding to at least three HLA class I molecules of the subject; (iii) determine the probability that a subject's tumor expresses one or more antigens corresponding to the T cell epitopes identified in step (ii) using the population expression data for each antigen, to identify the probability that the subject will have a clinical response to administering the pharmaceutical composition; and (iv) administering the composition of item 1 to the identified subject. 18. The method of item 17, where the subject has breast cancer.19. The method of item 17, where the pharmaceutical composition comprises 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, or more peptides, or 12 or more peptides.20. The method of item 17, wherein the pharmaceutical composition comprises 9 peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 92, 93, 98, 99-101 and 103-105.21. The method of item 17, wherein the pharmaceutical composition further comprises at least one additional peptide comprising a fragment of an antigen selected from PIWIL-2, AKAP-4, EpCAM, BORTS, HIWI, SPAG9, PLU-1, TSGA10, ODF -4, SP17, RHOXF-2, PRAME, NY-SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-All, HOM-TES-85 and NY-ESO-1.22. The method of item 21, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ ID NO: 1 to 20, 24 and 172 to 194.23. The method of item 21, wherein the fragment of an antigen comprises an amino acid sequence selected from any of SEQ ID NO:41-60 and 195-233.24. The method of item 17, where the pharmaceutical composition also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.25. The method of item 24, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone, Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, Toxin diphtheria (DT) and combinations of these. 26. The method of item 17 which further comprises administering a chemotherapeutic agent, a checkpoint inhibitor, a targeted therapy, radiation therapy, another immunotherapy, or a combination of these to the identified subject.27. The method of item 17 further comprising, prior to the administration step, (iii) performing an assay on a tumor sample from a subject to determine that the three or more peptides of the pharmaceutical composition comprise two or more different amino acid sequences, each of which is a. a fragment of a cancer-associated antigen expressed by cancer cells of the subject as determined in step (i); and b. a T cell epitope capable of binding to at least three HLA class I molecules from the subject; and (iv) confirm that the subject is likely to have a clinical response to the method of treatment. 28. A method for identifying and treating a human subject suffering from a cancer that is likely to have an immune response to the administration of a pharmaceutical composition according to item 1, wherein the method comprises (i) performing an assay on a biological sample of the subject to determine the HLA genotype of the subject; (ii) determines that the pharmaceutical composition comprises one or more sequences that are a T cell epitope capable of binding to at least three HLA class I molecules of the subject; and (iii) administering the composition of item 1 to the identified subject. 29. A kit comprising: a.a first pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any one of SEQ ID NO: 81-111 and 435 to 449; and b. a second different pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any of SEQ ID NO: 81-111 and from 435 to 449. 30. A pharmaceutical composition comprising: a nucleic acid molecule expressing two or more polypeptides, where each polypeptide comprises a fragment of up to 50 consecutive amino acids of an antigen selected from PIWIL-2, AKAP-4, EpCAM, BORIS, HIWI, SPAG9, PLU-1, TSGA10, ODF -4, SP17, RHOXF-2, PRAME, NY-SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-A11, HOM-TES-85 and NY-ESO-1, where each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 1 to 20, 24 and 172 to 194. 31. A pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a different sequence of the amino acid sequence of any of SEQ ID NO: 332-346.32. The pharmaceutical composition of item 31 comprising 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, more peptides, 12 or more peptides, 13 or more peptides, 14 or more peptides, or 15 or more peptides.33. The pharmaceutical composition of item 31 comprising 15 peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 332-346.34. The pharmaceutical composition of item 31 further comprising at least one additional peptide comprising a fragment of an antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL -3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3.35. Ua pharmaceutical composition of item 34, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 272-301.36. The pharmaceutical composition of item 34, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO:302-331.37. The pharmaceutical composition of item 31 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.38. The pharmaceutical composition of item 37, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone , Dinitrochlorobenzene (DNCB), Keyhole Limpet Hcmocyanin (KLH), Frcund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, diphtheria toxin (DT) and combinations of these. 39. A pharmaceutical composition comprising one or more nucleic acid molecules encoding one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any of SEQ ID NO: 332-346.40. The pharmaceutical composition of item 39, where the nucleic acid molecule(s) encode 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, or more peptides, 12 or more peptides, 13 or more peptides, 14 or more peptides, or 15 or more peptides.41. The pharmaceutical composition of item 39, wherein the nucleic acid molecule(s) encode 15 peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 332-346.42. The pharmaceutical composition of item 39, wherein the nucleic acid molecule(s) encode at least one additional peptide comprising a fragment of an antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1 , SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3.43. The pharmaceutical composition of item 42, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 272-301.44. The pharmaceutical composition of item 42, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO:302-331.45.The pharmaceutical composition of item 39 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.46. The pharmaceutical composition of item 45, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSE, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, levamisole, azimezone, isoprinisone , Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Ereund's Adjuvant (Complete), Ereund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, diphtheria toxin (DT) and combinations of these.47. A method of identifying and treating a human subject suffering from a cancer that is likely to have a clinical response to the administration of a pharmaceutical composition according to item 28, wherein the method comprises (i) testing a biological sample of the subject to determine the HLA genotype of the subject; (ii) determining that the pharmaceutical composition comprises two or more sequences that are a T cell epitope capable of binding to at least three HLA class I molecules of the subject; (iii) determining the probability that a tumor of the subject expresses one or more antigens corresponding to the T cell epitopes identified in step (ii) using the population expression data for each antigen, to identify the likelihood that the subject will have a clinical response to administration of the pharmaceutical composition; and (iv) administering the composition of item 28 to the identified subject. 48. The method of item 47, where the subject has ovarian cancer.49. The method of item 47, where the pharmaceutical composition comprises 2 or more peptides, 3 or more peptides, 4 or more peptides, 5 or more peptides, 6 or more peptides, 7 or more peptides, 8 or more peptides, 9 or more peptides, 10 or more peptides, or more peptides, 12 or more peptides, 13 or more peptides, 14 or more peptides, or 15 or more peptides.50. The method of item 47, wherein the pharmaceutical composition comprises 15 peptides, wherein each peptide comprises a different sequence of the amino acid sequences of SEQ ID NO: 332-346.51. The method of item 47, wherein the pharmaceutical composition further comprises at least one additional peptide comprising a fragment of an antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL -2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3.52. The method of item 51, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 272-301.53. The method of item 51, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO:302-331.54. The method of item 47, where the pharmaceutical composition also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.55. The method of item 54, where the adjuvant is selected from the group consisting of Montanide ISA-51, QS-21, GM-CSF, cyclophosamide, bacillus Calmette-Guerin (BCG), corynbacterium parvum, lcvamisole, azimczone, isoprinisone, Dinitrochlorobenzene (DNCB), Keyhole Limpet Hemocyanin (KLH), Freund's Adjuvant (Complete), Freund's Adjuvant (Incomplete), Mineral Gels, Aluminum Hydroxide (Alum), Lysolecithin, Pluronic Polyols, Polyanions, Oil Emulsions, Dinitrophenol, Toxin diphtheria (DT) and combinations of these. 56. The method of item 47 which further comprises administering a chemotherapeutic agent, a checkpoint inhibitor, a targeted therapy, radiation therapy, another immunotherapy, or a combination of these to the identified subject.57. The method of item 47 further comprising, prior to the administration step, performing an assay on a tumor sample from a subject to determine that the three or more peptides of the pharmaceutical composition comprise two or more different amino acid sequences, each of which is a a fragment of a cancer-associated antigen expressed by cancer cells of the subject as determined in step (i); and b. a T cell epitope capable of binding to at least three HLA class I molecules from the subject; and confirm that the subject is likely to have a clinical response to the method of treatment. 58.A method of identifying and treating a human subject suffering from a cancer that is likely to have an immune response to the administration of a pharmaceutical composition according to item 31, wherein the method comprises (i) assaying a biological sample from the subject for determining the HLA genotype of the subject; (ii) determining that the pharmaceutical composition comprises one or more sequences that are a T cell epitope capable of binding to at least three HLA class I molecules of the subject; and (iii) administering the composition of item 31 to the identified subject. 59. A kit comprising: a. a first pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any one of SEQ ID NO: 332-346; and b. a second different pharmaceutical composition comprising one or more peptides, wherein each peptide comprises a sequence different from the amino acid sequence of any of SEQ ID NO: 332-346. 60. A pharmaceutical composition comprising: a nucleic acid molecule that expresses two or more polypeptides, where each polypeptide comprises a fragment of up to 50 consecutive amino acids of an antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY- TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN, and AKAP-3, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 272-301 . EXAMPLES Example 1 - Process of HLA-epitope binding prediction and validation The predicted binding between HLA and particular epitopes (9-mer peptides) was based on the Immune Epitope Database tool for epitope prediction (www.iedb.org). The HLA I-epitope binding prediction process was validated by comparison with HLA I-epitope pairs determined by laboratory experiments. A data set of HLA I-epitope pairs reported in peer-reviewed publications or public immunological databases was compiled. The matching rate with the experimentally determined data set was determined (Table 2). The HLA I-binding epitope pairs in the dataset were correctly predicted with a probability of 93%. Coincidentally, HLA I-non-junctional epitope pairs were also correctly predicted with a probability of 93%. Table 2. Analytical specificity and sensitivity of the HLA-epitope binding prediction process. True epitopes (n=327) False epitopes (n=100) The accuracy of the prediction of multiple HLA binding epitopes was determined. Based on the analytical specificity and sensitivity using the 93% probability for true positive and true negative predictions and the 7% probability (=100% - 93%) for false positive and false negative prediction, the probability can be calculated. of the existence of a multiple HLA-binding epitope in a person. The probability of binding of multiple HLAs to an epitope shows the relationship between the amount of HLAs that bind to an epitope and the minimum expected amount of actual binding. According to the PEPI definition, three is the minimum expected number of HLAs to bind an epitope (bold). Table 3. Accuracy of predictions of multiple HLA binding epitopes. The validated HLA-epitope binding prediction process was used to determine all HLA-epitope binding pairs described in the examples below. Example 2 - Multiple HLA Epitope Presentation Predicts Cytotoxic T Lymphocyte (CTL) Response Presentation of one or more epitopes of a polypeptide antigen by one or more HLA I of an individual was determined to predict a CTL response. The study was carried out through a retrospective analysis of six clinical trials, carried out in 71 cancer patients and 9 HIV-infected patients (Table 4)1'7. Patients in these studies were treated with an HPV vaccine, three different NY-ESO-1-specific cancer vaccines, an HIV-1 vaccine, and a CTLA-4-specific monoclonal antibody (Ipilimumab) that was shown to reactivate CTL against the NY-ESO-1 antigen in patients with melanoma. All of these clinical trials measured antigen-specific CD8+ CTL responses (immunogenicity) in study subjects after vaccination. In some cases, a correlation between CTL responses and clinical responses was indicated. No patient was excluded from the retroactive study for any reason other than data availability. 157 patient data sets (Table 4) were randomized with a standard random number generator to create two independent cohorts for training and evaluation studies. In some cases, the cohorts contained multiple datasets from the same patient, resulting in a training cohort of 76 datasets from 48 patients and an evaluation / validation cohort of 81 datasets from 51 patients. *Number of patients used in the retrospective analysis of the original number of patients from clinical trials. **Immunoassays are based on the stimulation of T lymphocytes with groups of antigen-specific peptides and quantify the cytokines released by different techniques. CT: clinical trial; SBT: sequence-based typing; SSO: sequence-specific oligonucleotide; ICS: Intracellular cytokine staining; SSP: Sequence Specific Priming The indicated CTL responses from the training data sets were compared to the HLA I restriction profile of the epitopes (9 mers) of the vaccine antigens. HLA I genotype and antigen sequences of each patient were obtained from publicly available protein sequence databases or peer-reviewed publications and the HLA I-epitope binding prediction process was blinded to clinical CTL response data. from the patients. The number of epitopes of each antigen predicted to bind to at least 1 (PEPI1+), or at least 2 (PEPI2+), or at least 3 (PEPI3+), or at least 4 (PEPI4+), or at least 5 (PEPI5+) or all 6 (PEPI6) HLA class I molecules from each patient and the amount of bound HLA were used as classifiers for the indicated CTL responses. The true positive rate (sensitivity) and the true negative rate (specificity) were determined from the training data set for each classifier (amount of HLA bound) separately. ROC analysis was performed for each classifier. In a ROC curve, the true positive rate (sensitivity) was plotted against the false positive rate (1-specificity) for different cut-off points (Figure 1). Each point on the ROC curve represents a sensitivity / specificity pair corresponding to a particular decision threshold (epitope count (PEPI)). The area under the ROC curve (AUC) is a measure of how well the classifier can be distinguished between two diagnostic groups (CTL responder or non-responder). The analysis unexpectedly revealed that epitope presentation predicted by multiple HLA class I from a subject (PEPI2+, PEPI3+, PEPI4+, PEPI5+, or PEPI6), was in all cases a better predictor of CTL response than epitope presentation by only one or more HLA class I (PEPI1+, AUC = 0.48, Table 5). Table 5. Determination of the diagnostic value of the PEPI biomarker by ROC analysis. The CTL response of an individual was best predicted by considering epitopes of an antigen that could be presented by at least 3 HLA class I from an individual (PEPI3+, AUC=0.65, Table 5). The threshold PEPI3+ count (number of antigen-specific epitopes presented by 3 or more HLAs from an individual) that best predicted a positive CTL response was 1 (Table 6). In other words, at least one antigen-derived epitope is presented by at least 3 HLA class I from a subject (<1 PEPI3+), then the antigen can trigger at least one CTL clone and the subject is a CTL responder. probable. Using the <1 PEPI3+ threshold to predict potential CTL responders ("<1 PEPI3+ test") provided a diagnostic sensitivity of 76% (Table 12). Table 6. Determination of the <1 PEPI3+ threshold to predict potential CTL responders in the training dataset. Example 3 - Validation of the test for <1 PEPI3+ The test cohort of 81 data sets from 51 patients was used to validate the <1 PEPI3+ threshold for predicting an antigen-specific CTL response. For each data set in the test cohort, it was determined whether the <1 PEPI3+ threshold (at least one epitope derived from antigens presented by at least three HLA class I from the individual) was reached. This was compared to experimentally determined CTL responses indicated from clinical trials (Table 7). Clinical validation demonstrated that a PEPI3+ peptide induces a CTL response in an individual with a probability of 84%. 84% is the same value that was determined in the analytical validation of the prediction of PEPI3+, epitopes that bind to at least 3 HLA of an individual (Table 3). These data provide strong evidence that immune responses are induced by PEPT in individuals. Table 7. Diagnostic Performance Characteristics of the <1 PEPI3+ Assay (n=81). ROC analysis determined diagnostic accuracy, using the PEPI3+ count as cut-off values ​​(Figure 2). The AUC value = 0.73. For ROC analysis, an AUC of 0.7 to 0.8 was generally considered an objective diagnosis. A PEPI3+ count of at least 1 (<1 PEPI3+) best predicted a CTL response in the test data set (Table 8). This result confirmed the threshold determined during training (table 5). Table 8. Confirmation of <1 PEPI3+ threshold for predicting potential CTL responders in the test / validation data set. Example 4 - <1 PEPI3+ Test Predicts CD8+ CTL Reactivities The <1 PEPI3+ test was compared to a previously reported method for predicting a specific human CTL response to polypeptide antigens. The HLA genotypes of 28 VIN-3 and cervical cancer patients who received the HPV-16 synthetic long peptide vaccine (LPV) in two different clinical trials were determined from DNA samples8 8 9 10. LPV consists into long peptides covering the viral oncoproteins HPV-16 E6 and E7. The amino acid sequence of LPV was obtained from these publications. The publications also indicate the T cell responses of each vaccinated patient to the overlapping peptide pools of the vaccine. For each patient, the epitopes (9 mers) of LPV presented by at least three FILA class I patients (PEPI3+) and their distribution among the peptide pools were identified. Peptides comprising at least one PEPI3+ (<1 PEPI3+) were predicted to induce a CTL response. Peptides not comprising PEPI3+ were predicted not to induce a CTL response. The <1 PEPI3+ test correctly predicted 489 of 512 negative CTL responses and 8 of 40 positive CTL responses measured after vaccination (FIG. 3A). Overall, the agreement between the <1 PEPI3+ test and the experimentally determined CD8+ T cell reactivity was 90% (p<0.001). For each patient, the distribution between peptide groups of epitopes that are presented by at least one HLA class I patient (<1 PEPI1+, prediction of HLA-restricted epitopes, prior art method) was also determined. <1 PEPI1+ correctly predicted 116 of 512 negative CTL responses and 37 of 40 positive CTL responses measured after vaccination (FIG. 3B). Overall, the agreement between HLA-restricted epitope prediction (<1 PEPI1+) and CD8+ T cell reactivity was 28% (not significant). Example 5 - Prediction of TT class HLA-restricted CD4+ helper T cell epitopes 28 VIN-3 and cervical cancer patients receiving HPV-16 synthetic long peptide vaccine (LPV) in two different clinical trials (as described in Example 4) were investigated for helper CD4+ T responses. after vaccination with LPV (Figure 4A and 4B). The sensitivity of prediction of HLA class II restricted epitopes was 78%, as the next-generation tool predicted 84 positive responses (positive CD4+ T cell reactivity to a group of peptides for DP alleles from one person) of 107 (sensitivity = 78%). The specificity was 22% as it was able to rule out 7 negative responses out of 31. Overall, the agreement between HLA-restricted class II epitope prediction and CD4+ T cell reactivity was 66%, which is not statistically significant. significant. Example 6 - PEPI3+ <1 Test Predicts T-Cell Responses to Full-Length LPV Polypeptides Using the same studies reported as in Examples 4 and 5, the <1 ΡΕΡΙ3+ test was used to predict patient CD8+ and CD4+ T cell responses to the full-length E6 and E7 polypeptide antigens of the LPV vaccine. . Results were compared with experimentally determined responses and reported. The test correctly predicted CD8+ T-cell reactivity (PEPI3+) in 11 of 15 VIN-3 patients with positive CD8+ T-cell reactivity test results (sensitivity 73%, PPV 85%) and in 2 of 5 patients with cervical cancer (40% sensitivity, 100% PPV). CD4+ T cell reactivities (PEPI4+) correctly predicted 100% of VIN-3 and cervical cancer patients (Figure 5A, 5B, 5C and 5D). HLA class I and class II restricted PEPI3+ count was also found to correlate with the reported clinical benefit for LPV vaccinated patients. Patients with higher PEPI3+ counts had a complete or partial response after 3 months. Example 7 - Case Study pGX3001 is a DNA vaccine based on HPV16 containing full length E6 and E7 antigens with a linker in between. pGX3002 is a DNA vaccine based on HPV18 containing full length E6 and E7 antigens with a linker in between. A phase II clinical trial investigated the T cell responses of 17 HPV-infected patients with cervical cancer who were vaccinated with pGX3001 and pGX3002 (VGX-3100 vaccination)1. Figure 5A, 5B, 5C, 5D, 6A, 6B and 6C shows for two illustrative patients (patient 12-11 and patient 14-5) the position of each epitope (9mer) presented by at least 1 (PEPI1+), at least 2 (PEPI2+), at least 3 (PEPI3+), at least 4 (PEPI4+), at least 5 (PEPI5+), or all 6 (PEPI6) HLA class I of these patients within the full-length sequence of the two antigens of HPV-16 and the two antigens of HPV-18. Patient 12-11 had an overall PEPI1+ count of 54 for the combined vaccines (54 epitopes presented by one or more HLA class I). Patient 14-5 had a PEPI1+ count of 91. Therefore, patient 14-5 has a higher PEPI1+ count than patient 12-11 with respect to all four HPV antigens. PEPI1+ represent the distinct sets of HLA-restricted epitopes specific to vaccine antigens from patients 12-11 and 14-5. Only 27 PEPI1+ were common between these two patients. For PEPI3+ counts (number of epitopes presented by three or more patient HLA class I), the results for patients 12-11 and 14-5 were reversed. Patient 12-11 had a PEPI3+ count of 8, which includes at least one PEPI3+ on each of the four HPV16 / 18 antigens. Patient 14-5 had a PEPI3+ count of 0. The reported immune responses of these two patients were consistent with PEPI3+ counts, not PEPI1+ counts. Patient 12-11 developed immune responses to each of the four antigens after vaccination as measured by ELISpot, while patient 14-5 did not develop immune responses to any of the four vaccine antigens. A similar pattern was observed when the PEPI1+ and PEPI3+ pools of the 17 patients in the trial were compared. There was no correlation between PEPI1+ count and experimentally determined T cell responses indicated from the clinical trial. However, a correlation was observed between the T-cell immunity predicted by the <1 PEPI3+ test and the indicated T-cell immunity. The <1 PEPI3+ test predicted immune responders to the HPV DNA vaccine. Furthermore, the diversity of the patient's PEPI3+ pool resembled the diversity of T cell responses typically found in cancer vaccine trials. Patients 12-3 and 12-6, similar to patient 14-5, did not have PEPI3+ that predicted that the HPV vaccine could not activate T cell immunity. The rest of the patients had at least one PEPI3 that predicted the likelihood that HPV vaccine could activate T-cell immunity. 11 patients had multiple PEPI3+ predicting that HPV vaccine possibly activates polyclonal T-cell responses. Patients 15-2 and 15-3 were able to develop high magnitude T cell immunity to HPV E6, but low immunity to E7. Other patients 15-1 and 12-11 had the same magnitude response to E7 from HPV18 and HPV16, respectively. Example 8 - Design of a Model Population to Conduct In Silico Assays and Identify Candidate Precision Vaccine Targets for a Large Population An in silico human trial cohort of 433 subjects with full 4-digit HLA class I genotype (2 x HLA-A*xx:xx; 2 x HLA-B*xx:xx; 2 x HLA-C*xx:xx) and demographic information. This model population has subjects with mixed ethnicity who have a total of 152 different HLA alleles representing >85% of currently known G groups of alleles. A "large population" database containing 7,189 subjects characterized with a 4-digit HLA genotype and demographic information was also established. The large population has 328 different HLA class I alleles. The HLA allele distribution of the model population was significantly correlated with the large population (Table 9) (Pearson ρ< .001). Therefore, the model population of 433 patients represents a population 16 times larger. The model population represents 85% of the human race as provided by HLA diversity as well as HLA frequency. Table 9. Statistical analysis of HLA distributions in "model population" versus "large population". Example 9 - In silico assays based on the identification of multiple HLA-binding epitopes that predict T cell response rates reported from clinical trials The goal of this study is to determine if a model population, such as that described in Example 8, can be used to predict CTL reactivity rates of vaccines, ie, used in in silico efficacy assays. Twelve cancer antigen-derived peptide vaccines that induced T cell responses in a subpopulation of subjects were identified from peer-reviewed publications. These peptides have been investigated in clinical trials involving a total of 172 patients (4 ethnicities). T cell responses induced by the vaccine peptides have been determined from blood samples and are indicated. Immune response rate was determined as the percentage of study subjects with positive T cell responses measured in clinical trials (FIG. 7). The 12 peptides with the <1 PEPI3+ test were investigated in each of the 433 subjects in the model population described in Example 8. The "<1 PEPI3+ score" was calculated for each peptide as the proportion of subjects in the population model having at least one vaccine-derived epitope that can bind to at least three subject-specific HLA class I (<1 PEPI3+). If the corresponding clinical trial stratified patients for the selected population of HLA alleles, the model population was also filtered for subjects with the respective alleles (example: WT1, HLA-A*0201). Experimentally determined response rates reported in the trials were compared to PEPI3+ scores <1. The overall percentage of agreement (OPA) was calculated with the paired data (Table 11). A linear correlation was observed between the PEPI3+ score <1 and the response rate (R2 = 0.77) (Figure 7). This result shows that the identification of peptides that are predicted to bind to multiple HLAs from an individual is useful for in silico predicting the result of clinical trials. Table 11. Comparison of PEPI3+ <1 scores and CTL response rates of 12 peptide vaccines. Example 10. In silico assays based on the identification of multiple HLA-binding epitopes that predict T cell response rates reported from clinical trials II Nineteen clinical trials with published immune response rates (IRR) conducted with peptide- or DNA-based vaccines were identified (Table 19). These trials involved 604 patients (9 ethnicities) and covered 38 vaccines derived from tumor and viral antigens. Vaccine antigen-specific CTL responses were measured in each study patient, and the response rate in clinical study populations was calculated and reported. Each vaccine peptide from the 19 clinical trials was investigated with the <1 PEPI3+ test in each subject in the model population. The PEPI3+ score <1 for each peptide was calculated as the proportion of subjects in the model population having at least one vaccine-derived PEPI3+. Reported experimentally determined response rates from trials were compared to PEPI scores, as in Example 9 (Table 20). A linear correlation was observed between response rate and PEPI3+ score <1 (R2 = 0.70) (Figure 8). This result confirms that the identification of peptides that are predicted to bind to multiple HLAs in an individual can predict the T cell responses of subjects, and in silico assays can predict the outcome of clinical trials. Table 12. Published response rates in clinical trials. Table 13. Linear correlation between PEPI score and response rate (R2 = 0.7). Example 11 - In silico assay based on the identification of multiple HLA-binding epitopes in a multi-peptide vaccine that predicts the indicated immune response rate from clinical trials IMA901 is a therapeutic vaccine for renal cell cancer (RCC) that comprises 9 peptides derived from tumor-associated peptides (TUMAPs) that occur naturally in human cancer tissue. A total of 96 HLA-A*02+ subjects with advanced RCC were treated with IMA901 in two independent clinical studies (Phase I and Phase II). Each of the 9 peptides of IMA901 have been identified in the prior art as HLA-A2 restricted epitopes. Based on currently accepted standards, all are strong candidate peptides for enhancing T-cell responses against kidney cancer in trial subjects, since their presence has been detected in kidney cancer patients, and because trial patients are specifically selected to have at least one HLA molecule capable of presenting each of the peptides. For each subject in the model population, the amount of the nine IMA901 vaccine peptides that were capable of binding three or more HLAs was determined. As each peptide in the IMA901 vaccine is a 9mer, this corresponds to the PEPI3+ count. Results were compared to immune response rates reported in phase I and phase II clinical trials (Table 14). Table 14. Immune response rates in the model population and in two clinical trials to IMA901 *Number of patients tested for immune responses The results of the phase I and phase II study show the variability of immune responses to the same vaccine in different trial cohorts. In general, however, there was good agreement between the response rates predicted by the <2 PEPI3+ test and the reported clinical response rates. In a retrospective analysis, clinical investigators from the trials discussed above found that subjects who responded to multiple IMA901 vaccine peptides were significantly (p = 0.019) more likely to experience disease control (stable disease, partial response) than subjects who only responded to one peptide or who had no response. 6 of 8 subjects (75%) who responded to multiple peptides experienced clinical benefit in the trial, as opposed to 14% and 33% of 0 and 1 peptide responders, respectively. The phase II randomized trial confirmed that immune responses to multiple TUMAPs were associated with longer overall survival. As the presence of PEPI adequately predicted TUMAP responders, clinical responders to IMA901 are likely to be patients who may have <2 TUMAP PEPI. This subpopulation is only 27% of HLA-A*02 screened patients, and based on the clinical trial result, 75% of this subpopulation is expected to experience clinical benefit. The same clinical results suggest that 100% of patients experience clinical benefit if patient selection is based on TUMAP <3 PEPI, although this population would only represent 3% of the HLA-A*02 screened patient population. These results suggest that the rate of disease control (stable disease or partial response) is between 3% and 27% in the patient population investigated in clinical trials of IMA901. In the absence of a complete response, only a portion of these patients may have a survival benefit. These findings explain the lack of improved survival in the phase III clinical trial of IMA901. These results also demonstrated that HLA-A*02 enrichment of the study population was not sufficient to meet the primary overall survival endpoint in the Phase III IMA901 trial. As the IMA901 trial investigators noted, there is a need to develop a companion diagnostic (CDx) to screen for potential responders to peptide vaccines. These findings also suggest that selection of patients with <2 TUMAP-specific PEPIs may provide sufficient enrichment to demonstrate significant clinical benefit of IMA901. Example 12 - In silico assay based on the identification of multiple HLA-binding epitopes derived from vaccines that predict reported experimental clinical response rates A correlation was determined between the <2 PEPI3+ score of the immunotherapy vaccines determined in the model population described in Example 8 and the reported disease control rate (DCR, proportion of patients with complete and partial responses and stable disease). ) determined in clinical trials. Seventeen clinical trials conducted with peptide- and DNA-based cancer immunotherapy vaccines that have published disease control rates (DCR) or target response rate (ORR) were identified from peer-reviewed scientific journals (Table 15). These trials involved 594 patients (5 ethnicities) and covered 29 tumor and viral antigens. DCRs were determined according to the Response Evaluation Criteria in Solid Tumors (RECIST), which is the current standard for clinical trials, where clinical responses are based on changes in maximal cross-sectional dimensions42,43,44. In case DCR data were not available, objective response rate (ORR) data was used, which is also defined according to RECIST guidelines. Table 16 compares the PEPI3+ score <2 for each vaccine in the model population and the published DCR or ORR. A correlation between predicted and measured DCR was observed, providing further evidence that not only the immunogenicity, but also the potency of cancer vaccines depends on multiple HLA sequences of individuals (R2 = 0.76 ) (figure 9). Table 15. Selected clinical trials for disease control rate (DCR) prediction. Example 13 - Breast Cancer Vaccine Design for Large Population and Composition The PEPI3+ test described above was used to design peptides for use in breast cancer vaccines that are effective in a large percentage of patients, considering the heterogeneities of tumor antigens and HLA from patients. Breast cancer CTAs were identified and classified based on the overall expression frequencies of antigens found in colorectal cancer tumor samples as reported in peer-reviewed publications (Chen et al. Multiple Cancer / Testis Antigens Are Preferentially Expressed in Hormone-Receptor Negative and High-Grade Breast Cancers. Píos One 2011;6(3):el7876.; Kanojia et al. Sperm-Associated Antigen 9, a Novel Biomarker for Early Detection of Breast Cancer. Cancer Epidemiol Biomarkers Prev 2009;18(2) :630-639.; Saini et al. A Novel Cancer Testis Antigen, A-Kinase Anchor Protein 4 (AKAP4) Is a Potential Biomarker for Breast Cancer. Píos One 2013;8(2):e57095). Based on the ranked expression rate, the most frequently expressed CTAs were selected as target antigens for the breast cancer vaccine. The expression rates of selected breast cancer-specific CTAs are illustrated in Figure 11. To select target CTA immunogenic peptides, the PEPI3+ test and the model population described in Example 8 were used to identify the 9-mer epitopes (PEPI3+) that are most frequently presented by at least 3HLA of individuals in the model population. . We refer to these epitopes herein as "best EPI". An illustrative example of "PEPI3+ hotspot" analysis and identification of best EPIs is shown in Figure 10 for the PRAME antigen. The reported frequency of expression for each CTA was multiplied by the frequency of PEPI3+ sites of interest in the model population to identify T cell epitopes (9 mers) that will induce a cytotoxic T cell response against breast cancer antigens. in the highest proportion of individuals (table 17). Then, 15 mers spanning each of the 9 selected mers were selected (Table 17). The 15 mers were selected to bind the most HLA class II alleles from the most subjects, using the process described in Example 19 below. These 15 mers can induce CTL and T helper responses in the largest proportion of subjects. Table 17. List of best EPIs (underlined 9-mers) to select breast cancer peptides for vaccine composition. N%: frequency of antigen expression in colorectal cancers; B%: frequency of best EPIs, ie, the percentage of individuals with epitopes that bind to at least 3 HLA class I subjects in the model population (433 subjects); HLAII**: Percentage of individuals who have PEPI4+ specific for CD4+ T cells among normal donors (n=400); N%*B%: N% multiplied by B%. Thirty-one 30-mer peptides were then designed (Table 18a). Each of the 30 mers may consist of two optimized 15-mer fragments, usually of different common CTAs, arranged end-to-end, where each fragment comprises one of the 9 mers (best EPIs) from Table 17. Nine of these peptides were selected. of 30 mer for a panel of peptides, designated PolyPEPI915 (Table 18b). The expression frequencies for the 10 PolyPEPI915 target CTAs, individually or in combination, are shown in Figure 11. Table 18a. - 30mer Breast Cancer Vaccine Peptides Table 18b - Selected Breast Cancer Vaccine Peptides for the PolyPEPI915 Panel / Composition * Percentage of individuals who have PEPI3+-specific CD8+ T cells within the HLA class I model population (n=433). **Percentage of individuals who have PEPI4+-specific CD4+ T cells among normal donors (n=400). Characterization of PolyPEPI915 Tumor heterogeneity can be addressed by including peptide sequences that target multiple CTAs in an immunotherapy or vaccine regimen. The PolyPEPI915 composition targets 10 different CTAs. Based on the antigen expression rates for these 10 CTAs, the predicted average number of antigens expressed (AG50) and the minimum number of antigens expressed with 95% probability (AG95) on cancer cells were modeled. 95% of the individuals expressed a minimum of 4 of the 10 target antigens (AG95=4) as shown by the antigen expression curve in Figure 12A and 12B. The AG values ​​described above characterize a vaccine regardless of the patient population. They can be used to predict the probability that a specific cancer (eg, breast cancer) will express target antigens of a specific vaccine or immunotherapy composition. AG values ​​are based on known tumor heterogeneity, but do not consider HLA heterogeneity. The HLA heterogeneity of a certain population can be characterized from the point of view of a vaccine composition or immunotherapy by the number of antigens representing PEPI3+. These are the vaccine-specific CTA antigens for which <1 PEPI3+ is predicted, referred to herein as "AP". The average number of antigens with PEPI3+ (AP50) shows how the vaccine can induce an immune response against the target antigens of the composition (breast cancer vaccine-specific immune response). The PolyPEPI915 composition can induce an immune response against an average of 5.3 vaccine antigens (AP50=5.30) and 95% of the model population can induce an immune response against at least one vaccine antigen (AP95=1 )(figure 13A and 13B). Vaccines can be further characterized by AGP values ​​referring to "PEPI" antigens. This parameter is the combination of the two previous parameters: (1) AG depends on the frequencies of antigen expression in the specific tumor type but not on the HLA genotype of individuals in the population, and (2) AP depends on the genotype of HLA of the individuals in the population without considering the frequencies of expression of the antigen. AGP depends on the frequencies of expression of the vaccine antigens in the disease and the HLA genotype of the individuals in a population. Combining the AP and breast cancer AG data in the model population, the AGP value of PolyPEPI915 representing the probability distribution of vaccine antigens inducing immune responses against antigens expressed in breast tumors was determined. For PolyPEPI915, the AGP50 value in the model population is 3.37. AGP92=1 means that 92% of the subjects in the model population induce immune responses against at least one expressed vaccine antigen (FIG. 14A and 14B). Example 14 - Patient Screening Using Companion Diagnosis for Breast Cancer Vaccine The probability that a specific patient will have an immune response or a clinical response to treatment with one or more cancer vaccine peptides, eg, as described above, it can be determined based on (i) the identification of PEPI3+ within the vaccine peptides (9mer epitopes capable of binding to at least three patient HLAs); and / or (ii) a determination of target antigen expression in cancer cells from the patient, eg, as measured in a tumor biopsy. Ideally, both parameters are determined and the optimal combination of vaccine peptides is selected for use in treating the patient. However, PEPI3+ assays can be used only if a determination of expressed tumor antigens, for example by biopsy, is not possible, advisable, or unreliable due to biopsy error (i.e., tissue samples from biopsies taken from a small portion of the tumor or metastatic tumors do not represent the full repertoire of CTAs expressed in the patient). Example 15 - Comparison of PolyPEPI915 with Competing Breast Cancer Vaccines The in silico clinical trial model described above was used to predict immune response rates of the competitor breast cancer vaccines investigated in clinical trials (Table 19). . The immune response rate of these products was between 3% and 91%. Peptide vaccines alone were immunogenic in 3%-23% of individuals. By comparison, peptides having an amino acid sequence selected from SEQ ID NOs: 81-111 were immunogenic in between 44% and 73% of individuals in the same cohorts. This result represents a substantial improvement in the immunogenicity of each peptide of PolyPEPI915. The immune response rates of the competing combination peptide products were between 10-62%. The invented PolyPEPI915 combination products were 96% in the model population and 93% in a breast cancer patient population, representing an improvement in immunogenicity. Table 19. Predicted Immune Response Rates of Competing Breast Cancer Vaccines *Proportion of Subjects with ^1 PEPI3+ Another enhancement of the use of the PolyPEPI915 vaccine is the reduced chance of tumor escape.Each 30mer peptide in PolyPEPI915 targets 2 tumor antigens. CTLs against more tumor antigens are more effective against heterologous tumor cells than CTLs against a single tumor antigen. Another improvement of the PolyPEPI915 vaccine is that individuals who are likely to respond to vaccination can be identified based on their HLA genotype (sequence) and, optionally, antigen expression in their tumor using the methods described here. Pharmaceutical compositions with the PolyPEPI vaccines will not be administered to individuals whose HLA cannot present any PEPI3 from the vaccines. During clinical trials, correlation will be made between the mAGP or amount of AGP in the PolyPEPI915 regimen and the duration of the individuals' responses. A combination of vaccines with > 1 AGP is more likely to be needed to kill heterologous tumor cells. Pharmaceutical compositions with the PolyPEPI vaccines will not be administered to individuals whose HLA cannot present any PEPI3 from the vaccines. Example 16 Colorectal Cancer Vaccine Design and Composition Another example is shown for the colorectal cancer vaccine composition using the same design method demonstrated above. The PEPI3+ assay described above was used to design peptides for use in colorectal cancer vaccines that are effective in a large percentage of patients, considering the heterogeneities of patient HLAs and tumor antigens. Colorectal cancer CTAs were identified and classified based on the overall expression frequencies of antigens found in breast cancer tumor samples as reported in peer-reviewed publications (Figure 15) (Choi J, Chang H. The expression of MAGE and SSX Goossens-Beumer IJ, Zeestraten EC, Benard A, Christen T, Reimers MS, Keijzer R, Sier CF , Liefers GJ, Morreau H, Putter H, Vahrmeijer AL, van de Velde CJ, Kuppen PJ. Clinical prognostic value of combined analysis of Aldhl, Survivin, and EpCAM expression in colorectal cancer. Br J Cancer 2014. 110(12):2935 -2944.; Li M, Yuan YH, Han Y, Liu YX, Yan L, Wang Y, Gu J. Expression profile of cancer-testis genes in 121 human colorectal cancer tissue and adjacent normal tissue. Clinical Cancer Res 2005. 11( 5): 1809-1814). Based on the ranked expression rate, the most frequently expressed CTAs were selected as target antigens for colorectal cancer vaccine. The expression rates of selected breast cancer-specific CTAs are illustrated in Figure 15. To select immunogenic peptides from the most frequently expressed colorectal cancer CTAs, the PEPI3+ assay and the model population described in Example 8 were used to identify the "best EPIs". The reported frequency of expression for each CTA (N%) was multiplied by the frequency of PEPI3+ sites of interest in the model population (B%) to identify T cell epitopes (9 mers) that will induce an immune response against CTAs. colorectal cancer antigens in the largest proportion of individuals (table 20). Then, 15 mers spanning each of the 9 selected mers were selected (Table 20). The 15 mers were selected to bind the greatest number of HLA class II alleles from the majority of subjects, using the process described in Example 19 below. These 15 mers can induce CTL and T helper responses in the largest proportion of subjects. Table 20. List of best EPIs (underlined 9-mers) to select colorectal cancer peptides for vaccine composition. N%: frequency of antigen expression in colorectal cancers; B%: frequency of best EPIs, ie, the percentage of individuals with epitopes that bind to at least 3 HLA class I subjects in the model population (433 subjects); HLAII**: Percentage of individuals who have PEPI4+ specific for CD4+ T cells among normal donors (n=400); N%*B%: N% multiplied by B%. Thirty-one 30-mer peptides were then designed (Table 21a). Each of the 30 mers consists of two optimized 15-mer fragments, usually from different frequent CTAs, where each 30 mer usually contains at least one high-frequency HLA class II-binding PEPI. The 15-mer fragments are arranged end-to-end, each comprising one of the 9 mers (Best EPI) from Table 20 as described above. Nine of these 30mer peptides were selected for a panel of peptide vaccines, designated PolyPEPI1015 (Table 21b). The expression frequencies for the 8 target CTAs of PolyPEPI1015, individually or in combination, are shown in Figure 15. Table 21a - 30mer Colorectal Cancer Vaccine Peptides * Percentage of individuals who have PEPI3+ specific for CD8+ T cells within the model population (n=433). **Percentage of individuals who have PEPI4+-specific CD4+ T cells among normal donors (n=400). Table 21b - Selected Colorectal Cancer Vaccine Peptides for Composition of PolyPEPI1015 * Percentage of individuals who have PEPI3+ specific for CD8+ T cells within the model population (n=433). **Percentage of individuals who have PEPI4+-specific CD4+ T cells among normal donors (n=400). Characterization of PoliPEP11015 colorectal cancer vaccine Tumor heterogeneity: The PolyPEPI1015 composition targets 8 different CTAs (FIG. 15). Based on the antigen expression rates for these 8 CTAs, AG50=5.22 and AG95=3, Figure 16A and 16B. Patient heterogeneity: AP50=4.73 and AP95=2 (AP95=2) (figure 17A and 17B). Tumor and patient heterogeneity: AGP50 = 3.16 and AGP95 = 1 (model population) (figure 18A and 18B). Example 17 - Comparison of Colorectal Cancer Vaccine Peptides with Competing Colorectal Cancer Vaccines The in silico clinical trial model described above was used to determine the T cell responder rate of the latest generation CRC peptide vaccines and currently developed and compared with that of polyPEPI1015 (Table 22). The PEPI3+ test demonstrates that competing vaccines can induce immune responses against a tumor antigen in a fraction of subjects (2% - 77%). However, determination of multi-antigen responses (multi-PEPI) for the 2 competing multi-antigen vaccines resulted in no or 2% responders. *E1% Responders is the proportion of subjects in the model population with HLAI 1<PEPI3+ (CD8+ T cell responses) to 1, 2, 3, 4, or 5 antigens of the vaccine compositions. As multi-PEPI responses correlate with tumor vaccine-induced clinical responses, it is unlikely that any of the competing vaccines will demonstrate clinical benefit in 98% of patients. In contrast, multi-PEPI responses were predicted in 95% of subjects, suggesting the likelihood of clinical benefit in most patients. Table 22 Predicted Immune Response Rates of PolyPEPI1015 and Competing Colorectal Cancer Vaccines Example 18 Ovarian Cancer Vaccine Design and Composition The PEPI3+ test was used to design peptides for use in ovarian cancer vaccines essentially using the same design method described in examples 13 and 16 above. The frequency of reported CTA expression associated with ovarian cancer (N%) was multiplied by the frequency of PEPI3+ sites of interest in the model population (B%) to identify T cell epitopes (9 mers) that will induce a response. immune against ovarian cancer antigens in the largest proportion of individuals (Table 23). Then, 15 mers spanning each of the 9 selected mers were selected (Table 23). The 15 mers were selected to bind the greatest number of HLA class II alleles from the majority of subjects, using the process described in Example 20 below. Table 23. List of best EPIs (underlined 9-mers) to select ovarian cancer peptides for vaccine composition. N%: frequency of antigen expression in colorectal cancers; B%: frequency of best EPIs, ie, the percentage of individuals with epitopes that bind to at least 3 HLA class I subjects in the model population (433 subjects); HLAII**: Percentage of individuals who have PEPI4+ specific for CD4+ T cells among normal donors (n=400); N%*B%: N% multiplied by B%. Then 15 peptides of 30 mer were designed (Table 24). Table 24 - 30mer Ovarian Cancer Vaccine Peptides * Percentage of individuals having CD8+ T-cell-specific PEPI3+ within the model population (n=433). **Percentage of individuals who have PEPI4+-specific CD4+ T cells among normal donors (n=400). Example 19 Efficacy of Exemplary Design Procedure for PolyPEPI1018 Colorectal Cancer Vaccine Current baseline CRC treatment options in patients identified as potential responders using an accompanying in vitro diagnostic (CDx) test. There are current clinical trials in the United States and Italy to evaluate PolyPEP11018 in patients with metastatic colorectal cancer. The product contains 6 peptides (6 of the 30mer peptides of PolyPEPI1015 described in examples 16 and 17) mixed with the adjuvant Montanide. 6 peptides were selected to induce T cell responses against 12 epitopes of 7 testicular cancer antigens (CTAs) that are most frequently expressed in CRC. 6 peptides were optimized to induce long-lasting CRC-specific T cell responses. Potentially responsive patients with T-cell responses against multiple CTAs expressed in the tumor with an accompanying diagnosis (CDx) can be selected. This example establishes the precision process used to design PoliPEPI1018. This process can be applied to design vaccines against other cancers and diseases. A. Selection of Multiple Antigen Targets The selection of tumor antigens is essential for the safety and efficacy of cancer vaccines.The characteristic of a good antigen is to have a restricted expression in normal tissues to avoid autoimmunity. Several categories of antigens meet this requirement, including uniquely mutated antigens (eg, p53), viral antigens (eg, human papillomavirus antigens in cervical cancer), and differentiation antigens (eg, CD20 in B-cell lymphoma). The inventors selected multiple testicular cancer antigens (CTA) as target antigens since they are expressed on various types of tumor cells and testis cells, but are not expressed on any other normal tissue or somatic cell. CTAs are desirable targets for vaccines for at least the following reasons: • tumors of higher histological grade and later clinical stage tend to have higher frequency of CTA expression • only a subpopulation of tumor cells expresses a certain CTA • different types of cancer are significantly different in their frequency of CTA expression• tumors that are positive for one CTA often present simultaneous expression of more than one CTA• None of the CTAs appear to be cell surface antigens, therefore, these are exclusive targets for vaccines against the cancer (not suitable targets for antibody-based immunotherapies) To identify target CTAs for PolyPEPI1018, the inventors created a CTA expression database. This database contains CTAs that are expressed in CRCs ranked in order of rate of expression. Correlation studies by the inventors (see Example 11) suggest that vaccines that induce CTL responses against multiple antigens that are expressed on tumor cells may benefit patients. Therefore, seven CTAs with high expression rates in CRC were selected for inclusion in P0IÍPEPIIOI8 development. Details are presented in Table 25. Table 25 Target CTA in P0IÍPEPIIOI8 CRC Vaccine Name Characterization Rate of CTA Expression Testis-specific protease-like protein 50 is an oncogene that induces cell proliferation, cell invasion and growth tumor. It is frequently expressed in TSP50 89.47% gastric, breast, cervical, and colorectal cancer samples; and is infrequently expressed in normal human tissues, except in testis spermatocytes. Epithelial cell adhesion molecule is a tumor-associated antigen, which is expressed in colon cancers and overexpressed in EpCAM 88.35% in various human carcinomas. The high expression of EpCAM on cancer-initiating stem cells makes it a valuable target for cancer vaccines. EpCAM is also expressed in normal epithelial cells at low or negligible levels, with the exception of squamous epithelium, hepatocytes, and keratinocytes. Survivin (baculoviral IAP repeat-containing protein 5) is a multitasking protein that promotes cell proliferation and inhibits apoptosis. Although it is strongly expressed in fetal tissues and is required for normal development, it is not expressed in most adult tissues. Survivin is expressed in various cancers, including carcinomas. Normal tissues that express survivin at low levels include the thymus, CD34+ bone marrow-derived stem cells, and basal colonic epithelium. Strong overexpression of Survivin 87.28% 1 r r survivin compared to normal tissues was observed in tumors of lung, breast, colon, stomach, esophagus, pancreas, bladder, uterus, ovaries, large cell non-Hodgkin's lymphoma, leukemias, neuroblastoma , melanoma and non-melanoma skin cancers. The cancer-associated gene 1 protein is a typical CTA, which might play a role in cell proliferation and tumorigenesis. CAGE1 is strongly expressed in colorectal cancer tissues and weakly expressed in adjacent normal colorectal mucosa. Furthermore, CAGE1 74.47% CAGE1 is expressed in melanoma, hepatoma and breast tumors. Expression of CAGE1 protein is not detected in healthy human tissues, beyond the testis. Sperm-associated antigen 9 participates in c-Jun N-terminal kinase signaling and acts as a scaffolding protein, thus playing an important role in cell survival, proliferation, apoptosis, and tumor development.SPAG9 expression 74.36% of SPAG9 was detected in patients with epithelial ovarian cancer (90%), breast cancer (88%), cervical cancer (82%), renal cell cancer (88%), and colorectal cancer (74%). None of the adjacent noncancerous tissues showed antigen expression. SPAG9 expression is restricted to the testis. FBXO39 (BC.P-20) is a testis-specific protein and is an important part of the E3 ubiquitin ligase complex. It participates in ubiquitination and regulation of the cell cycle, immune responses, signaling, and proteasome degradation of proteins. FBXO39 is expressed in colon and breast cancers. The expression of FBXO39 has also been detected in the ovary, placenta and FBXO39 38.60% lung. FBXO39 expression is 100-fold higher in testes and 1000-fold higher in colorectal cancers compared to normal tissue. The role of melanoma-associated antigen 8 is unknown, although it may play a role in embryonic development and tumor transformation or aspects of tumor progression. The MAGEA8 gene 43.75% MAGE-A8 is expressed in CRC and in hepatocellular carcinoma. The expression of MAGE-A8 in normal tissues is restricted to the testes and the placenta. B. Precise Targeting Is Achieved by PEPI3+ Biomarker-Based Vaccine Design As described above, the PEPI3+ biomarker predicts the subject's vaccine-induced T cell responses. The inventors developed and validated a test to accurately identify PEPIs from HLA genotypes and antigen sequences (Examples 1, 2, 3). The PEPI test algorithm was used to identify the dominant PEPIs (best EPIs) of the 7 target CTAs to be included in the PolyPEPI1018 CRC vaccine. Dominant PEPIs identified with the process described herein can induce CTL responses in the highest proportion of subjects: i. Identification of all HLA class I binding PEPIs of the 7 CTA targets in each of the 433 subjects in the model population ii. Identification of the dominant PEPIs (best EPIs) that are PEPIs present in the largest subpopulation. The 12 dominant PEPIs that are derived from the 7 CTAs in PolyPEPI1018 are presented in Table 26. The % PEPI in the model population indicates the proportion of 433 subjects with the indicated PEPI, that is, the proportion of subjects where the indicated PEPI can induce CTL responses. There is a very high variability (18% - 78%) in the dominant PEPIs in inducing CTL responses despite the optimization steps used in the identification process. Table 26 CRC-Specific HLA Class I Binding Dominant PEPIs in P0IÍPEPIIOI8 The inventors optimized each dominant PEPI to bind the majority of HLA class II alleles from the majority of subjects. This should improve efficacy as it induces CD4+ T helper cells that can augment CD8+ CTL responses and contributes to long-lasting T cell responses. The example presented in Figure 4A and 4B demonstrates that PEPIs that bind to ééé3 HLA class II alleles most likely activate helper T cells. The 15-mer peptides selected with the process described herein contain dominant HLA class I and class II binding PEPIs. Therefore, these peptides can induce CTL and T helper responses in the highest proportion of subjects. Process: 1. HLA class II genotyping of 400 normal donors*2. Extension of each 9-mer dominant PEPI (Table 20) on both sides with amino acids matching the source antigen3. HLA class II PEPI prediction of 400 normal donors using an IEDB4 algorithm. Selection of 15-mer peptide with the highest proportion of subjects having HLA class II binding PEPI5. Ensuring the presence of a dominant HLA class II PEPI in each vaccine peptide by linking two 15-mer peptides The 12 optimized 15-mer peptides derived from the 7 CTAs in PolyPEPI1018 are presented in Table 27. These peptides have different HLA class II binding characteristics. There is high variability (0%-100%) in PEPI generating ability (^3 HLA binding) between these peptides despite such optimized custom vaccine design.Table 27 Antigen-specific HLA class II binding PEPI in PolyPEPI1018 30-mer vaccine peptides have the following advantages compared to shorter peptides: (i) Multiple precisely selected tumor-specific immunogens: each 30-mer contains two precisely selected cancer-specific immunogenic peptides that are capable of inducing CTL and T helper responses in the majority of the relevant population (similar to the model population).(ii) Ensure natural antigen presentation. Long 30-mer polypeptides can be viewed as prodrugs: They are not biologically active by themselves, but are processed into smaller peptides (9 to 15 amino acids in length) that are loaded onto HLA molecules of professional antigen-presenting cells. . Antigen presentation resulting from long peptide vaccination reflects physiological pathways for presentation on HLA class I and class II molecules. Furthermore, the processing of long peptides in cells is much more efficient than that of large intact proteins.(iii) They exclude the induction of tolerant T cell responses. The 9-mer peptides do not require processing by professional antigen-presenting cells and therefore bind exogenously to HLA class I molecules. Thus, the injected short peptides bind in large numbers to HLA class I molecules. HLA class I of all nucleated cells that have surface HLA class I. In contrast, long peptides from >20-mers are processed by antigen-presenting cells prior to binding to HLA class I. Thus, vaccination with long peptides is less likely to lead to tolerance and promote the desired antitumor activity. .(iv) Induce long-lasting T cell responses as they can stimulate responses of. Helper T cells by binding to multiple HLA class II molecules (v) Utility. The GMP manufacturing, formulation, quality control and administration of a smaller number of peptides (each with all of the above characteristics) is more feasible than a larger number of peptides that provide different characteristics. Each 30-mer peptide in PolyPEPI1018 consists of 2 dominant HLA class I binding PEPIs and at least one strong HLA class II binding PEPI. Strong-binding PEPIs bind 4 HLA class II alleles in >50% of individuals. Thus, the vaccine peptides are tailored to both HLA class I and class II alleles of individual subjects in a general population (which is a population relevant to the design of CRC vaccines). As previously demonstrated, the high variability of HLA genotype in subjects causes a high variability of P0IIPPEPIIOI8-induced T cell responses. This justifies the co-development of a CDx that determines potential responders. The PEPI3+ and >2PEPI3+ biomarkers were able to predict the immune response and clinical responses, respectively, of PolyPEPI1018 vaccinated subjects as detailed in Examples 11 and 12. These biomarkers will be used to co-develop a CDx that predicts potential vaccine responders against CRC of PolyPEPI1018. Example 20 - Analysis of the composition and immunogenicity of the PolyPEPI1018 CRC vaccine The peptides selected for the composition of PolyPEPI1018 are shown in Table 28. Table 28 - Selected Colorectal Cancer Vaccine Peptides for P0IÍPEPIIOI8 Composition * Percentage of individuals having PEPI3+ binding to HLA class I within the model population (n=433). **Percentage of individuals who have PEPI3+ binding to HLA class II within the model population (n=433). The PolyPEPI1018 peptides are formulated in two mixtures, MIX1 containing the peptides of SEQ ID: 130, 131 and MIX2 containing the peptides of SEQ ID: 121, 124, 134, 126. MIX 1 and MIX 2 can be administered sequentially. Characterization of immunogenicity The inventors used the PEPI3+ assay to characterize the immunogenicity of PolyPEPI1018 in a cohort of 37 CRC patients with full HLA genotyping data. T cell responses were predicted in each patient against the same 9mer peptides that will be used in clinical trials. These peptides represent the 12 dominant PEPI3+ peptides within PolyPEPI1018. The 9 mers are shown in table 26. The specificity and sensitivity of PEPI3+ prediction depends on the actual amount of HLA predicted to bind a particular epitope. Specifically, the inventors determined that the probability of an HLA-restricted epitope inducing a T-cell response in a subject is typically 4%, which explains the low sensitivity of state-of-the-art prediction methods based on epitope prediction. HLA-restricted. Applying the PEPI3+ methodology, the inventors determined the probability that the T cell response to each dominant PEPI3+-specific is induced by PolyPEPI1018 in the 37 CRC patients. The results of this analysis are summarized in Table 29. Table 29 Probability of PEPI dominant in the 6 peptides of PolyPEPI1018 in 37 patients with CRC Abbreviations: CRC = colorectal cancer; PEPI = personal epitope Note: Percentages represent the probability of PolyPEPI1018-induced CD8+ T cell responses. Overall, these results show that the most immunogenic peptide in P0IÍPEPIIOI8 is CRC-P8, which is predicted to bind >3 HLA in the majority of patients. The least immunogenic peptide, CRC-P3, binds >1 HLA in many patients and has a 22% chance of inducing T-cell responses. Because the bioassays used to detect T-cell responses are less precise than PEPI3+, this estimate may be the most accurate characterization of T-cell responses in CRC patients. Although MAGE-A8 and SPAG9 were immunogenic in the model population used for vaccine design, MAGE-A8-specific PEPI3+ were absent in all 37 CRC patients, and only one patient (3%) had SPAG9-specific PEPI3+. Further characterization of the predicted PolyPEPI1018 response rate in the model population described in Example 8 and in 295 CRC patients with known HLA class I genotypes is shown in Tables 30 and 31. Table 30 - PolyPEPI1018 Response Rates in the Model Population (433 Normal Donors) Table 31 - PolyPEPI1018 Response Rates for 295 CRC Patients Characterization of toxicity - immunoBLAST A method was developed that can be performed on any antigen to determine its potential to induce a toxic immune reaction, such as autoimmunity. The method is referred to herein as immunoBLAST. PolyPEPI1018 contains six 30-mer polypeptides. Each polypeptide consists of two 15-mer peptide fragments derived from antigens expressed on CRC. Neoepitopes can be generated at the junction region of the two 15-mer peptides and can induce unwanted T cell responses against healthy cells (autoimmunity). This is evaluated using the immunoBLAST methodology. A 16-mer peptide was designed for each of the 30-mer components of PolyPEP1018. Each 16-mer contains 8 amino acids from the end of the first 15 residues of the 30-mer and 8 amino acids from the start of the second 15 residues of the 30-mer—precisely thus spanning the joining region of the two 15-mers. These 16-mers are then analyzed to identify cross-reactive regions of local similarity to human sequences using BLAST (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi), which compares protein sequences to bases of sequence data and calculates the statistical significance of the matches. 8-mers within the 16-mers were selected as the test length as that length represents the minimum length required for a peptide to form an epitope, and is the distance between anchor points during HLA binding. As shown in Figure 19, amino acid positions in a polypeptide are numbered. The starting positions of the putative HLA-binding and neoepitope-forming 9-mer peptides are the 8 amino acids at positions 8-15. The initial positions of the peptides derived from tumor antigens harbored by the 15-mer that can form the pharmaceutically active epitopes are 7+7=14 amino acids at position 1-7 and 16-22. The proportion of potential peptides generating neoepitopes is 36.4% (8 / 22). The PEPI3+ test was to identify neoepitopes and neoPEPI among the 9-mer epitopes in the junction region. The risk of P0IIPPEPIIOI8 inducing unwanted T cell responses in the 433 subjects in the model population was assessed by determining the proportion of PEPI3+ subjects among the 9-mer in the junction region. The result of the neoepitope / neoPEPI analysis is summarized in Table 32. Across the 433 subjects in the model population, the average predicted number of epitopes that could be generated by intracellular processing was 40.12. Neoepitopes were frequently generated; 11.61 of 40.12 (28.9%) epitopes are neoepitopes. Most of the peptides could be identified as a neoepitope, but the number of subjects presenting neoepitopes varied. The epitopes harbored by P0IÍPEPIIOI8 create an average of 5.21 PEPI3+. These PEPIs can activate T cells in a subject. The number of possible neoPEPIs was much lower than the number of neoepitopes (3.7%). There is a small possibility that these neoPEPIs may compete for T cell activation with PEPIs in some subjects. Importantly, activated neoPEPI-specific T cells did not target healthy tissue. Table 32 - Identification of possible neoepitopes of P0IÍPEPIIOI8 Abbreviations: CRC = colorectal cancer; HLA = human leukocyte antigen; PEPI = personal epitope Each of the 30-mer peptides in PolyPEPI1018 were released for clinical development as none of the 8-mer in the binding regions matched any human protein except the target CTAs. Characterization of activity / efficacy The inventors have developed pharmacodynamic biomarkers to predict the activity / effect of vaccines in individual human subjects as well as in populations of human subjects. These biomarkers facilitate more efficient vaccine development and also lower the cost of development. Inventors have the following tools: Antigen Expression Database: The inventors have collected data from experiments published in peer-reviewed scientific journals on tumor antigens expressed by tumor cells and organized by tumor type to create a database of CTA expression levels - database of CTA (CTADB). As of April 2017, the CTADB contained data from 145 CTAs of 41,132 tumor samples, and was organized according to the frequencies of CTA expression in the different types of cancer. In Silico Test Populations: The inventors have also collected data on the HLA genotypes of several different model populations. Each individual in the populations has a complete 4-digit HLA genotype and ethnic data. The populations are summarized in Table 33. Table 33 In silico test populations Abbreviations: CRC = colorectal cancer; HLA = human leukocyte antigen Using these tools (or potentially equivalent databases or model populations), the following markers can be assessed: • GA95 - potency of a vaccine: the amount of antigens in a cancer vaccine that a specific tumor type expresses with a 95 % probability. AG95 is an indicator of vaccine potency and is independent of the immunogenicity of the vaccine antigens. AG95 is calculated from tumor antigen expression rate data, which is collected in the CTADB. Technically, AG95 is determined from the CTA binomial distribution, and considers all possible variations and expression rates. In this study, AG95 was calculated by accumulating the probabilities of a given number of expressed antigens, over the widest range of antigens where the sum of probabilities was less than or equal to 95%. The correct value is between 0 (no expression expected with 95% probability) and maximum number of antigens (all antigens expressed with 95% probability). probability). • PEPI3+ count - immunogenicity of a vaccine in a subject: Vaccine-derived PEPI3+ are signature epitopes that induce T cell responses in a subject. PEPI3+ can be determined using the PEPI3+ test in subjects whose full 4-digit HLA genotype is known. • PA Count - Antigenicity of a Vaccine in a Subject: Amount of PEPI3+ vaccine antigens. Vaccines such as PoliPEPI1018 contain antigen sequences expressed on tumor cells. The PA count is the number of antigens in the vaccine that contain PEPI3+, and the PA count represents the number of antigens in the vaccine that can induce T cell responses in a subject. The AP count characterizes the subject's vaccine antigen-specific T cell responses as it depends only on the subject's HLA genotype and is independent of the subject's disease, age, and medication. The correct value is between 0 (no PEPI presented by the antigen) and the maximum number of antigens (all antigens present PEPI).• AP50 - antigenicity of a vaccine in a population: The mean number of vaccine antigens with a PEPI in a population. The AP50 is suitable for the characterization of vaccine antigen-specific T cell responses in a given population since it is dependent on the HLA genotype of subjects in a population. Technically, the PA count was calculated in the model population and the binomial distribution of the result was used to calculate the PA50. • AGP count - efficacy of a vaccine in a subject: amount of vaccine antigens expressed in the tumor with PEPI . The AGP count indicates the amount of tumor antigens that the vaccine recognizes and induces a T-lymphocyte response against them (achieves the target). The AGP count depends on the rate of expression of the vaccinia antigen in the subject's tumor and the subject's HLA genotype. The correct value is between 0 (no PEPI presented by the expressed antigen) and the maximum number of antigens (all antigens are expressed and present a PEPI).• AGP50 - efficacy of a cancer vaccine in a population: the amount Mean number of vaccine antigens expressed on PEPI-indicated tumor (ie, AGP) in a population. The AGP50 indicates the mean amount of tumor antigens that can be recognized by vaccine-induced T cell responses. AGP50 depends on the expression rate of the antigens in the indicated tumor type and the immunogenicity of the antigens in the target population. AGP50 can estimate vaccine efficacy in different populations and can be used to compare different vaccines in the same population. The calculation of AGP50 is similar to that used for AG50, except that expression is weighted by the occurrence of PEPI3+ in the subject at expressed vaccine antigens. In a theoretical population, where each subject has a PEPI of each vaccine antigen, the AGP50 will be equal to AG50. In another theoretical population, where no subject has a PEPI from any vaccine antigen, the AGP50 will be 0. In general, the following statement is valid: 0 > AGP50 > AG50. • mAGP - a candidate biomarker for the selection of potential responders: the probability that a cancer vaccine will induce T cell responses against multiple antigens expressed in the indicated tumor. mAGP is calculated from the expression rates of vaccine antigens in CRC and the presence of vaccine-derived PEPI in the subject. Technically, based on the AGP distribution, the mAGP is the sum of the probabilities of the multiple AGPs (<2 AGPs). Application of these markers to evaluate the antigenicity and efficacy of PolyPEPI1018 in individual patients with CRC Table 34 shows the antigenicity and efficacy of PolyPEPI1018 in 37 CRC patients using AP and AGP50, respectively. As expected from the high variability of PolyPEPI1018-specific T cell responses (see Table 29), AP and AGP50 have high variability. The most immunogenic antigen in P0IÍPEPIIOI8 was FOXO39; each patient had a PEPT3+. However, FOXO39 is expressed in only 39% of CRC tumors, suggesting that 61% of patients will have FOXO39-specific T cell responses that do not recognize the tumor. The least immunogenic antigen was MAGE-A8; none of the 37 CRC patients had a PEPI3+ even though the antigen was expressed in 44% of CRC tumors. These results illustrate that both the expression and the immunogenicity of antigens can be considered when determining the efficacy of a cancer vaccine. AGP50 indicates the mean amount of antigens expressed in CRC tumor with PEPI. Patients with higher AGP50 values ​​are more likely to respond to P0I1PEPIIOI8 as higher AGP50 values ​​indicate that the vaccine may induce T cell responses against more antigens expressed on CRC cells. The last column in Table 32 shows the probability of mAGP (multiple AGP; ie, at least 2 AGP) in each of the 37 CRC patients. The average mAGP in CRC patients is 66%, suggesting that there is a 66% chance that a CRC patient will induce T-cell responses against multiple tumor-expressed antigens. Table 34 - Antigenicity (AP count), Efficacy (AGP50 count) and mAGP of PolyPEPI1018 in 37 patients with CRC Abbreviations: CRC = colorectal cancer; PEPI = personal epitope; CTA = testicular cancer antigen; AP = antigens expressed with <1 PEPI These biomarkers have immediate utility in vaccine development and routine clinical practice as they do not require invasive biopsies. Antigen expression data can be obtained from the achieved tumor sample and can be organized in databases. 4-digit HLA genotyping can be performed from a saliva sample. It is a validated test performed by certified laboratories around the world for paternity and transplant testing. These evaluations will allow drug developers and clinicians to gain deeper insights into the immunogenicity and activity of the tumor response and the potential emergence of resistance. Application of these markers to assess the antigenicity and efficacy of PolyPEPI1018 in populations Antigenicity of PolyPEPI1018 CRC Vaccine in a General Population The antigenicity of PolyPEPIlOL 8 in a subject is determined by the AP count, which indicates the amount of vaccine antigens that induce T cell responses in a subject. The P0IÍPEPIIOI8 AP count was determined in each of the 433 subjects in the model population using the PEPI test, and then the AP50 count was calculated for the model population. As shown in Figure 20, the AP50 of PolyPEPI1018 in the model population is 3.62. Therefore, the mean number of immunogenic antigens (ie, antigens with <1 PEPI) on PolyPEPI1018 in a general population is 3.62. Efficacy of PolyPEPI1018 CRC Vaccine in a General Population Vaccine-induced T cells can recognize and kill tumor cells if the tumor cell presents a PEPI in the vaccine. The amount of AGP (PEPI-expressed antigens) is an indicator of vaccine efficacy in an individual, and depends on the potency and antigenicity of PolyPEPI1018. As shown in Figure 21, the mean number of immunogenic CTAs (ie, APs [antigens expressed with <1 PEPI]) on PolyPEPI1018 is 2.54 in the model population. The probability that PolyPEPI1018 will induce T-cell responses against multiple antigens in one subject (ie, mAGP) in the model population is 77%. Comparison of PolyPEPI1018 CRC Vaccine Activities in Different Populations Tables 35 to 37 show the comparison of the immunogenicity, antigenicity and efficacy of PolyPEPIlOl 8 in different populations. Table 35 - Comparison of immunogenicity, antigenicity and efficacy of PolyPEPIlOl8 in different subpopulations Abbreviations: CRC = colorectal cancer; PEPI = personal epitope; SD = standard deviation; PA = expressed antigens with <1 PEPI Average amount of PEPI3+ and AP results demonstrate that PolyPEPI1018 is highly immunogenic and antigenic in all populations; Ρ0Ι1ΡΕΡΠΟΙ8 can induce an average of 3.7-6.0 clones of CRC-specific T cells against 2.9-3.7 CRC antigens. The immunogenicity of PolyPEPI 1018 was similar in CRC patients and the average population (p>0.05), this similarity may be due to the small sample size of the CRC population. Additional analyzes suggest that PolyPEPI1018 is significantly more immunogenic in a Chinese population compared to an Irish population or a general population (p<0.0001). Differences in immunogenicity are also reflected in vaccine efficacy as characterized by AGP50; PolyPEPI1018 is more effective in a Chinese population and less effective in an Irish population. Because a CDx will be used to screen for potential PolyPEPI1018 responders, ethnic differences will only be reflected in the higher percentage of Chinese individuals who might be eligible for treatment compared to Irish individuals. Table 36 - PolyPEPI1018 CRC Vaccine, Predicted Immune Response Rates Against Multiple CRC Antigens Table 37 - PolyPEPI1018 CRC Vaccine, Predicted Immune Response Rates Against Multiple CRC Antigens Example 21 - Personalized immunotherapy composition for the treatment of ovarian cancer This example describes the treatment of a patient with ovarian cancer with a personalized immunotherapy composition, where the composition was designed specifically for the patient based on her HLA genotype according to the description described herein. This example and Example 22 below provide clinical data to support the principles regarding the binding of epitopes across multiple HLAs of a subject to induce a cytotoxic T-lymphocyte response on which the present disclosure is based. The HLA class I and class II genotype of the patient with XYZ metastatic ovarian adenocarcinoma was determined from a saliva sample. To develop a personalized pharmaceutical composition for patient XYZ, thirteen peptides were selected, each of which met the following two criteria: (i) derived from an antigen expressed in ovarian cancers, as reported in peer-reviewed scientific publications; and (ii) comprises a fragment that is a T cell epitope capable of binding to at least three HLA class I from patient XYZ (Table 38). In addition, each peptide is optimized to bind to the maximum amount of HLA class II in the patient. Table 38: XYZ Ovarian Cancer Patient Personalized Vaccine Eleven PEPI3 peptides in this immunotherapy composition can induce XYZ T cell responses with 84% probability and the two PEPI4 peptides (POC01-P2 and POCOl-P5) with 98% probability, according to validation of the PEPI test shown in Table 3. T cell responses are directed at 13 antigens expressed on ovarian cancers. Expression of these cancer antigens in patient XYZ was not evaluated. Instead, the probability of successful cancer cell killing was determined based on the probability of antigen expression on the patient's cancer cells and the positive predictive value of the test of <1 PEPI3+ (AGP count). The AGP count predicts the efficacy of a vaccine in a subject: amount of vaccine antigens expressed in the tumor (ovarian adenocarcinoma) of the patient with PEPI. The AGP count indicates the amount of tumor antigens that the vaccine recognizes and induces a T cell response against the patient's tumor (hits the target). The AGP count depends on the rate of expression of the vaccinia antigen in the subject's tumor and the subject's HLA genotype. The correct value is between 0 (no PEPI presented by the expressed antigen) and the maximum number of antigens (all antigens are expressed and present a PEPI). The probability that patient XYZ expresses one or more of the 12 antigens is shown in Fig. Figure 22. AGP95 = 5, AGP50 = 7.9, mAGP = 100%, AP = 13. A pharmaceutical composition for patient XYZ may be composed of at least 2 of the 13 peptides (Table 38), since it was determined that the presence in an immunotherapy or vaccine composition of at least two polypeptide fragments (epitopes) that can bind at least three HUA from an individual (<2 PEPI3+) predicts a clinical response. Peptides are synthesized, dissolved in a pharmaceutically acceptable solvent, and mixed with an adjuvant prior to injection. It is desirable that the patient receive personalized immunotherapy with at least two peptide vaccines, but it is preferable to increase the probability of killing cancer cells and decrease the possibility of relapse. For the treatment of patient XYZ, the 12 peptides were formulated as 4 x 3 / 4 peptide (POCOl / 1, POCOl / 2, POCOl / 3, POCOl / 4). A treatment cycle is defined as the administration of the 13 peptides in 30 days. Patient History: Diagnosis: metastatic ovarian adenocarcinoma Age: 51 Family history: colon and ovarian cancer (mother), breast cancer (grandmother) Tumor pathology: BRCal-185delAG, BRAF-D594Y, MAP2K1-P293S, NOTCH1-S2450N • 2011: first diagnosis of ovarian adenocarcinoma; Wertheim operation and chemotherapy; lymph node removal • 2015: Metastases in pericardial adipose tissue, excised • 2016: Liver metastases • 2017: Retroperitoneal and mesenteric lymph nodes have progressed; early peritoneal carcinomatosis with accompanying small ascites Previous therapy: • 2012: Paclitaxel-carboplatin (6x)• 2014: Caelyx-carboplatin (lx)• 2016-2017 (9 months): Lymparza (Olaparib) 2x400 mg / day, oral• 2017: Hycamtin inf. 5x2.5 mg (3x one scric / mcs), treatment with ΡΓΓ vaccine started on April 21, 2017. Table 39 Peptide Treatment Schedule for Patient XYZ Patient's Tumor MRI Findings (Onset April 15, 2016) • Disease was primarily confined to the liver and lymph nodes. Use of MRI limits detection of lung (lung) metastases• May 2016 - January 2017: Olaparib treatment• 25 / Dec / 2016 (prior to PIT vaccine treatment) There was a dramatic reduction in tumor burden with confirmation of the response obtained in FU2• January - March 2017 - TOPO Protocol (topoisomerase)• April 6, 2017 FU3 demonstrated the reappearance of existing lesions and the appearance of new lesions that lead to disease progression• April 21, 2017 INITIAL PIT• Jul 21 / 17 (after 2nd PIT cycle) FU4 demonstrated continued growth of lesions, general enlargement of the pancreas and abnormal parapancreatic signal along with increased ascites• Jul 26 / 17 - CBP+Gem+Avastin• 20 / Sep / 17 (after 3 cycles of PIT) FU5 demonstrated reversal of lesion growth and improved pancreatic / parapancreatic signal. Findings suggest pseudoprogression• Nov 28 / 17 (after 4 cycles of PIT) FU6 demonstrated best response with resolution of non-target lesions The MRI data for patient XYZ is shown in Table 40 and Figure 23. Table 40. Injury Response Compendium Table Example 22 Design of personalized immunotherapy composition for the treatment of breast cancer The HLA class I and class II genotype of the ABC metastatic breast cancer patient was determined from a saliva sample. To develop a personalized pharmaceutical composition for patient ABC, twelve peptides were selected, each of which met the following two criteria: (i) derived from an antigen expressed in breast cancers, as reported in peer-reviewed scientific publications; and (ii) comprises a fragment that is a T cell epitope capable of binding to at least three HLA class I from patient ABC (Table 41). In addition, each peptide is optimized to bind to the maximum amount of HLA class II in the patient. The twelve peptides target twelve breast cancer antigens. The probability that patient ABC expresses one or more of the 12 antigens is shown in Figure 24. Table 41. 12 peptides for the ABC breast cancer patient Predicted efficacy: AGP95=4; 95% probability that the PIT vaccine induces CTL responses against 4 CTAs expressed in BRC09 breast cancer cells. Additional efficacy parameters: AGP50 = 6.3, mAGP = 100%, AP = 12. Efficacy detected after vaccination with the 12 peptides: 83% reduction in tumor metabolic activity (PET CT data). For the treatment of patient ABC, the 12 peptides were formulated as 4x3 peptide (PBR01 / 1, PBR01 / 2, PBR01 / 3, PBR01 / 4). A treatment cycle is defined as the administration of the 12 different peptide vaccines in 30 days. Patient History Diagnosis: bilateral metastatic breast carcinoma: right breast is ER positive, PR negative, Her2 negative; the left breast is ER, PR, and Her2 negative. First diagnosis: 2013 (4 years before treatment with the PIT vaccine) 2016: extensive metastatic disease with lymph node involvement both above and below the diaphragm. Multiple liver and lung metastases. 2016-2017 treatment: Etrozole, Ibrance (Palbociclib) and Zoladex Results Mar 7 2017: before treatment with PIT vaccine Hepatic multi-metastatic disease with real extrinsic compression of the origin of the common bile duct and massive dilatation of the entire intrahepatic biliary tract. Celiac, hilar hepatic and retroperitoneal adenopathy May 26, 2017: after 1 PIT cycle Detected efficacy: 83% reduction in tumor metabolic activity (PET CT), liver, lung, lymph nodes and other metastases. Safety detected: skin reactions Local swelling at the injection site within 48 hours of vaccine administration Follow-up: BRC-09 was treated with 5 cycles of PIT vaccine. She was feeling very well and refused PET CT in September 2017. In November she developed symptoms, PET scan showed progressive disease, but refused all treatments. Also, the oncologist discovered that he had not taken Palbocyclib since the spring / summer. Patient ABC passed away in January 2018. It is likely that the combination of pablocyclib and the personalized vaccine was responsible for the remarkable rapid response observed after administration of the vaccine. Palbocyclib has been shown to enhance the activity of immunotherapies by increasing HLA presentation of CTAs and decreasing Treg proliferation: (Goel et al. Nature. 2017:471-475). The PIT vaccine can be used as an adjunct to next-generation therapy for maximum efficacy. Example 23 - Composition of personalized immunotherapy for the treatment of a patient with metastatic breast cancer in advanced stage Patient BRC05 was diagnosed with inflammatory breast cancer on the right with extensive carcinomatous lymphangiosis. Inflammatory breast cancer (IBC) is a rare but aggressive form of locally advanced breast cancer. It is called inflammatory breast cancer because its main symptoms are swelling and redness (the breast often looks swollen). Most inflammatory breast cancers are invasive ductal carcinomas (start in the milk ducts). This type of breast cancer is associated with the expression of high-risk human papillomavirus oncoproteins1. In fact, HPV16 DNA was diagnosed in this patient's tumor. Patient stage in 2011 (6 years prior to PIT vaccine treatment): T4: Tumor of any size with direct extension to the chest wall and / or skin (ulceration or skin nodules) pN3a: Metastases in < 10 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm); or metastases to infraclavicular (level III axillary lymph nodes). 14 vaccine peptides were designed and prepared for patient BRC05 (Table 42). Peptides PBRC05-P01-P10 were prepared for this patient based on population expression data. The last 3 peptides in Table 42 (SSX-2, MORC, MAGE-B1) were designed from antigens whose expression was measured directly in the patient's tumor. Table 42 - Vaccine peptides for patient BRC05 Note: bold and red means CDS PEPI, underlined means best binding CD4 allele. T cell responses in peripheral mononuclear cells were measured 2 weeks after 1st vaccination with the peptide mixture PBRCO5_P1, PBRC05_P2, PBRC05_P3, PBRC05_P4, PBRC05_P5, PBRCO5_P6, PBRC05_P7. Table 43 - Antigen-Specific T-Cell Responses: Number of Points / 300,000 PBMC The results show that a single immunization with 7 peptides induced strong T cell responses against 3 of the 7 peptides, demonstrating strong MAGE-A11, NY-SAR-35, FSIP1 and MAGE-A9 specific T cell responses. There were weak responses against AKAP4 and NY-BR-1, and no response against SPAG9. References 1 Bagarazzi et al. Immunotherapy against HPV16 / 18 generates potent TH1 and cytotoxic cellular immune responses. Science Translational Medicine. 2012; 4(155):155ral38.2 Gudmundsdotter et al. Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial. Vaccine. 2011; 29(33):5558-66. 3 Bioley et al. HLA class I - associated immunodominance affects CTL responsiveness to an ESO recombinant protein tumor antigen vaccine. Clin Cancer Res. 2009; 15(1):299-306.4 Valmori et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody / Thl responses and CD8 T cells through cross-priming. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(21):8947-52.5 Yuan et al. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Nati Acad Sci USA. 2011;108(40):16723-16728.6 Kakimi et al. A phase I study of vaccination with NY-ESO-lf peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen.Int J Cancer. 2011;129(12):2836-46.7 Wada et al. Vaccination with NY-ESO-1 overlapping peptides mixed with Picibanil OK-432 and montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen. J Immunother. 2014;37(2):84-92.8 Welters et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin. Cancer Res. 2008; 14(1):178-87.9 Kenter et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl I Med. 2009; 361(19):1838-47.10 Welters et al. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. PNAS. 2010; 107(26): 11895-9.11 http: / / www.ncbi.nlm.nih.gov / projects / gv / mhc / main.fcgi?cmd=initThe MHC database, NCBI (accessed 7 Mar 2016). 12 Karkada et al. Therapeutic vaccines and cancer: focus on DPX-0907. Biologics. 2014;8:27-38.13 Butts et al. Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. J Clin Oncol. 2005;23(27):6674-81.14 Yuan et al. Safety and immunogenicity of a human and mouse gplOO DNA vaccine in a phase I trial of patients with melanoma. Cancer Immun. 2009;9:5.15 Kovjazin et al. ImMucin: a novel therapeutic vaccine with promiscuous MHC binding for the treatment of MUC1-expressing tumors. Vaccine. 2011;29(29-30):4676-86.16 Cathcart et al. Amultivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia.Blood. 2004;103:1037-1042. 17 Chapuis et al. Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transit Med. 2013;5(174):174ra27.18 Keilholz et al. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood; 2009; 113(26):6541-8.19 Walter et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. NatMed. 2012; 18(8):1254-61.20 Phuphanich et al. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013;62(l):125-35.21 Kantoff et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099-105.22 Tagawa et al. Phase I study of intranodal delivery of a plasmid DNA vaccine for patients with StagelV melanoma. Cancer. 2003;98(l):144-54.23 Slingluff et al. Randomized multicenter trial of the effects of melanoma-associated helper peptides and cyclophosphamide on the immunogenicity of a multipeptide melanoma vaccine. J Clin Oncol. 2011;29(21):2924-32.24 Kaida et al. Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer. J Immunother. 2011;34(1):92-9.25 Fenoglio et al. A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer. Cancer Immunol Immunother; 2013; 62:1041-1052.26 Krug et al. WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer. Cancer Immunol Immunother; 2010; 59(10):1467-79.27 Slingluff et al. Clinical and immunological results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells.J Clin Oncol; 2003; 21(21):4016-26.28 Hodi et al. Improvcd survival with ipilimumab in patients with metastatic melanoma. N Engl J Med; 2010;363(8):711-23.29 Carmon et al. Phase I / Π study exploring ImMucin, a pan-major histocompatibility complex, anti-MUCl signal peptide vaccine, in multiple myeloma patients. Br J Hematol. 2014; 169(1):44-56. 30 http: / / www.merckgroup.com / en / media / extNewsDetail.html?newsId=EB4A46A2AC4A52E7C1257AD9001F3186&newsType=l(accessed 28 Mar 2016)31 Trimble et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 controlled proteins for cervical intraepithelial neoplasia 2 / 3: a randomized, double-blind, placebo-phase 2b trial. Lancet. 2015;386(10008):2078-88.32 Cusi et al. Phase I trial of thymidylate synthase poly epitope peptide (TSPP) vaccine in advanced cancer patients. Cancer Immunol Immunother; 2015; 64:1159-1173.33 Asahara et al. Phase I / II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transit Med; 2013; 11:291.34 Yoshitake et al. Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS. Clin Cancer Res; 2014;21(2):312-21.35 Okuno et al. Clinical Trial of a 7-Peptide Cocktail Vaccine with Oral Chemotherapy for Patients with Metastatic Colorectal Cancer. Anticancer Res; 2014; 34: 3045-305.36 Rapoport et al. Combination Immunotherapy after ASCT for Multiple Myeloma Using MAGE-A3 / Poly-ICLC Immunizations Followed by Adoptive Transfer of Vaccine-Primed and Costimulated Autologous T Cells. Clin Cancer Res; 2014; 20(5): 1355-1365.37 Greenfield et al. A phase T dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2 / 3. Oncoimmunol; 2015; 4:10, el031439.38 Snyder et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371(23):2189-99.39 Van Allen et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science; 2015; 350:6257.40 Li et al. Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood; 2001; 98:3241-324841 Takcdatsu et al. Determination of Thrombopoietin-Dcrivcd Pcptidcs Rccognizcd by Both Cellular and Humoral Immunities in Healthy Donors and Patients with Thrombocytopenia. 2005; 23(7): 975-98242 Eisenhauer et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer; 2009; 45(2):228-47. 43 Therasse et al. New guidelines to evaluate the response to treatment in solid tumors: European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Cañada. J Nati Cancer Inst; 2000; 92:205-216.44 Tsuchida & Therasse. Response evaluation criteria in solid tumors (RECIST): New guidelines. Med Pediatr Oncol. 2001; 37:1-3.45 Durie et al. International uniform response criteria for multiple myeloma. Leukemia; 2006;20:1467-1473.

Claims

1. A polypeptide comprising a fragment of up to 50 consecutive amino acids from (a) a colorectal cancer-associated antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, LEMD1, MAGE-A8, MAGE-A6, and MAGE-A3, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 21 to 40 and 234 to 250; (b) an ovarian cancer-associated antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN, and AKAP-3, wherein the fragment comprises the amino acid sequence from any of SEQ ID NO: 272 to 301; and / or(c) a breast cancer-associated antigen selected from PIWIL-2, AKAP-4, EpCAM, BORIS, HIWI, SPAG9, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, PRAME, NY-SAR-35, MAGE-A9, NY-BR-1, SURVIVIN, MAGE-A11, HOM-TES-85 and NY-ESO-1, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 1 to 20, 24 and 172 to 194;where, optionally, the fragment is flanked at the N and / or C end by additional amino acids that are not part of the sequence of the antigen associated with breast, ovarian, or colorectal cancer.

2. The polypeptide of claim 1, wherein polypeptide a. is a fragment of a colorectal cancer-associated antigen selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3, and LEMD1, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 21 to 40 and 234 to 250; ob. comprises or consists of two or more fragments of one or more colorectal cancer-associated antigens selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3, and LEMD1, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 21 to 40 and 234 to 250, wherein, optionally, the fragments overlap or are arranged end-to-end in the polypeptide; or.is a fragment of an ovarian cancer-associated antigen selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN, and AKAP-3, wherein the fragment comprises an amino acid sequence selected from any of SEQ ID NO: 272 to 301; or d. comprises or consists of two or more fragments of one or more ovarian cancer-associated antigens selected from PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OYTES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 272 to 301, wherein, optionally, the fragments overlap or are arranged end-to-end in the polypeptide; e.g.is a fragment of a breast cancer-associated antigen selected from SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM-TES-85, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, wherein the fragment comprises the amino acid sequence of any of SEQ ID NO: 1 to 20, 24 and 172 to 194; of. comprises or consists of two or more fragments of one or more breast cancer-associated antigens selected from SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM-TES-8, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2, wherein each fragment comprises a different amino acid sequence selected from any of SEQ ID NO: 1 to 20, 24 and 172 to 194; wherein, optionally, the fragments are overlapped or arranged end-to-end in the polypeptide.

3. The polypeptide according to claim 1 or claim 2, wherein the polypeptide comprises or consists of fragments of at least two different cancer-associated antigens, wherein the cancer-associated antigens are selected from (a) TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, MAGE-A8, MAGE-A6, MAGE-A3 and LEMD1; (b) PIWIL-4, WT1, EpCAM, BORIS, AKAP-4, OY-TES-1, SP17, PIWIL-2, PIWIL-3, SPAG9, PRAME, HIWI, SURVIVIN and AKAP-3; and / or(c) SPAG9, AKAP-4, BORIS, NY-SAR-35, NY-BR-1, SURVIVIN, MAGE-A11, PRAME, MAGE-A9, HOM-TES-8, PIWIL-2, EpCAM, HIWI, PLU-1, TSGA10, ODF-4, SP17, RHOXF-2; wherein each fragment comprises a different amino acid sequence selected from SEQ ID NO: 21 to 40 and 234 to 250; SEQ ID NO: 272 to 301; and / or SEQ ID NO: from 1 to 20, 24 and from 172 to 194.

4. The polypeptide according to any of claims 1 to 3 comprising or consisting of one or more amino acid sequences selected from SEQ ID NO: 41-80, 251 to 271, 302 to 331 and 196 to 233.

5. The polypeptide according to any of claims 1 to 4 comprising or consisting of the amino acid sequence from any of SEQ ID NO: 81 to 142, 332 to 346 and 435-449.6.A panel of two or more polypeptides according to any one of claims 1 to 5, wherein (a) each polypeptide comprises a different amino acid sequence selected from SEQ ID NO: 21 to 40 and 234 to 250; or (b) each polypeptide comprises a different amino acid sequence selected from SEQ ID NO: 272 to 301; or (c) each peptide comprises a different amino acid sequence selected from SEQ ID NO: 1 to 20, 24 and 172 to 194; or (d) each peptide comprises a different amino acid sequence selected from SEQ ID NO: 1 to 40, 234 to 250, 272 to 301 and 172 to 194.

7. The polypeptide panel according to claim 6 comprising six peptides having the amino acid sequences SEQ ID NO: 130, 121, 131, 124, 134, 126.

8. A pharmaceutical composition or kit having one or more polypeptides according to any of claims 1 to 5, a polypeptide panel according to claim 6 or claim 7, or a polypeptide comprising at least two amino acid sequences selected from SEQ ID NO: 21 to 40 and 234 to 250; SEQ ID NO: 272 to 301; and / or SEQ ID NO: 1 to 20, 24 and 172 to 194 as an active ingredient.

9. A method of vaccination, immunotherapy, or induction of a cytotoxic T lymphocyte response in a subject, wherein the method comprises administering to the subject a pharmaceutical composition according to claim 8.

10. The method of claim 9, which is a method for treating cancer, optionally colorectal cancer, ovarian cancer, or breast cancer.

11. A method for identifying a human subject likely to have a cytotoxic T-cell response to the administration of a pharmaceutical composition according to claim 8, wherein the method comprises (i) determining that the polypeptides of the active ingredient of the pharmaceutical composition comprise a sequence that is a T-cell epitope capable of binding to at least three class I HLA molecules of the subject; and (ii) identifying that the subject is likely to have a cytotoxic T-cell response to the administration of the pharmaceutical composition.

12. The method of claim 11 further comprising using population expression data for each antigen that (a) is selected from TSP50, EpCAM, SPAG9, CAGE1, FBXO39, SURVIVIN, LEMD1, MAGE-A8, MAGE-A6, MAGE-A3, PIWIL-4, WT1, BORIS, AKAP-4, OY-TES-1, SP17, PIWTL-2, PIWTL-3, PRAME, HIWT, PLU-1, TSGA10, ODF-4, RHOXF-2, NY-SAR-35, MAGE-A9, NY-BR-1, MAGE-A11, HOM-TES-85, NY-ESO-1 and AKAP-3; and (b) comprises an amino acid sequence that is i. a peptide fragment of the active ingredient of the pharmaceutical composition; and ii. a T lymphocyte epitope capable of binding to at least three HLA class I molecules of the subject; to determine the likelihood that the subject will have a cytotoxic T lymphocyte response directed against one or more polypeptide antigens expressed by cancer cells of the subject.

13. A method for identifying a subject likely to have a clinical response to a treatment method according to claim 10, wherein the method comprises (i) determining that the polypeptides of the active ingredient of the pharmaceutical composition comprise two or more different amino acid sequences, each of which is a. a T-cell epitope capable of binding to at least three HLA class I molecules of the subject; and b. a fragment of a cancer-associated antigen expressed by cancer cells of the subject, wherein, optionally, the cancer-associated antigen is present in a sample obtained from the subject; and (ii) identifying that the subject is likely to have a clinical response to the treatment method.

14. A method for determining the probability of a specific human subject having a clinical response to a treatment method according to claim 10, wherein one or more of the following factors correspond to a higher probability of a clinical response: (a) presence in the polypeptides of the active ingredient of a greater number of amino acid sequences and / or different amino acid sequences that are each a T-cell epitope capable of binding to at least three class I HLA of the subject; (b) a greater number of target polypeptide antigens comprising at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B.is a T lymphocyte epitope capable of binding to at least three class I HLA of the subject; wherein, optionally, the target polypeptide antigens are expressed in the subject, and wherein, furthermore, optionally, the target polypeptide antigens are found in one or more samples obtained from the subject; (c) a higher probability of the subject expressing target polypeptide antigens, optionally a threshold amount of the target polypeptide antigens and / or optionally target polypeptide antigens that have been determined to comprise at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B.is a T-cell epitope capable of binding to at least three class I HLAs of the subject; and / or (d) a greater number of target polypeptide antigens predicted to be expressed by the subject, optionally a greater number of target polypeptide antigens that the subject expresses with a threshold probability, and / or optionally target polypeptide antigens that have been determined to comprise at least one amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B. is a T-cell epitope capable of binding to at least three class I HLAs of the subject.

15. The method of claim 14, wherein the method comprises (i) identifying which target polypeptide antigens of the active ingredient polypeptides comprise an amino acid sequence that A. is comprised in a polypeptide of the active ingredient; and B. is a T-cell epitope capable of binding to at least three class I HLA of the subject; (ii) using population expression data for each antigen identified in step (i) to determine the probability that the subject expresses one or more of the antigens identified in step (i) that together comprise at least two different amino acid sequences from step (i); and (iii) determining the probability that the subject will have a clinical response to administration of the pharmaceutical composition, kit, or polypeptide panel, wherein a higher probability determined in step (ii) corresponds to a more probable clinical response.

16. The method of claim 15, wherein the at least two different amino acid sequences are comprised within the amino acid sequence of two different target polypeptide antigens of the active ingredient polypeptides.

17. The method of any of claims 13 to 16 further comprising selecting or recommending the administration of the pharmaceutical composition as a method of treatment for the subject and, optionally, treating the subject by administering the pharmaceutical composition.

18. A treatment method according to claim 10, wherein it has been identified that the subject is likely to have a clinical response or has a minimal probability above a threshold of having a clinical response to the treatment by means of a method according to any of claims 13 to 16.

19. The method of any of claims 9, 10, 17 and 18, wherein the treatment is administered in combination with chemotherapy, targeted therapy or checkpoint inhibitors. 20.A method for identifying a human subject who is unlikely to have a clinical response to a treatment method according to claim 10, wherein the method comprises (i) determining that the peptides of the active ingredient of the pharmaceutical composition do not comprise two or more different amino acid sequences, each of which is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject; and (iii) identifying that the subject is likely to have a clinical response to the treatment method.