CUSTOMIZED IMMUNOGENIC PEPTIDE IDENTIFICATION PLATFORM

Abstract

The description relates to methods for identifying polypeptide fragments that are immunogenic to a specific human subject, methods for preparing customized pharmaceutical compositions comprising such polypeptide fragments, subject-specific pharmaceutical compositions comprising such polypeptide fragments, and treatment methods using such compositions. The methods include identifying a polypeptide fragment that binds to multiple HLA receptors of the subject.

Description

PERSONALIZED IMMUNOGENIC PEPTIDE IDENTIFICATION PLATFORM COUNTRYSIDE The disclosure relates to methods for predicting whether a polypeptide is immunogenic for a specific human subject, methods for identifying fragments of a polypeptide that are immunogenic for a specific human subject, methods for preparing precision or customized pharmaceutical compositions or kits comprising said fragments. of polypeptides, specific pharmaceutical compositions for a human subject comprising said polypeptide fragments, and methods of treatment using said compositions. BACKGROUND For decades, scientists have assumed that chronic disease was beyond the reach of a person's natural defenses. Recently, however, a significant number of tumor regressions observed in individuals treated with antibodies that block immune-inhibiting molecules has accelerated the field of cancer immunotherapy. These clinical findings demonstrate that reactivation of existing T cell responses results in significant clinical benefit for individuals. These advances have renewed enthusiasm for the development of cancer vaccines that induce tumor-specific T cell responses. Despite the promise, current immunotherapy is effective in only a fraction of individuals. Furthermore, most cancer vaccine trials have failed to demonstrate statistically significant efficacy due to a low rate of tumor regression and anti-tumor T cell responses in individuals. Similar failures have been reported with therapeutic and preventive vaccines that sought to include T cell responses in the field of HIV and allergies. There is a need to overcome the clinical failures of immunotherapies and vaccines. 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 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. Thus, fragments of a polypeptide antigen that are immunogenic for a specific individual are those that can be bind to multiple HLA class I (activate cytotoxic T cells) or class II (activate helper T cells) expressed by that individual. Accordingly, in a first aspect, the disclosure provides methods for predicting whether a polypeptide or polypeptide fragment is immunogenic for a specific human subject, wherein the methods comprise the steps of (i) determining whether the polypeptide comprises: (a ) an amino acid sequence that is a T cell epitope capable of binding to at least two HLA class I molecules of the subject; or (b) an amino acid sequence that is a T cell epitope capable of binding to at least two HLA class II molecules from the subject; and (ii) predicting A. that the polypeptide is immunogenic for the subject if the polypeptide comprises at least one sequence that meets the requirements of step (i); oB. that the polypeptide is not immunogenic for the subject if the polypeptide does not comprise at least one sequence that meets the requirements of step (i). The description also provides methods for identifying a fragment of a polypeptide as immunogenic for a specific human subject, wherein the methods comprise the steps of (i) determining that the polypeptide comprises: (a) an amino acid sequence that is an epitope of lymphocytes T capable of binding to at least two HLA class I molecules from the subject; or (b) an amino acid sequence that is a T cell epitope capable of binding to at least two HLA class II molecules from the subject; and (ii) identifying said sequence as a fragment of the polypeptide that is immunogenic for the subject. In some embodiments, the methods of the disclosure comprise the step of determining or obtaining the HLA class I genotype and / or the HLA class II genotype of the specific human subject. A specific polypeptide antigen may comprise more than one fragment that is a T cell epitope capable of binding multiple HLAs from a specific individual. The combined set of all these fragments characterizes the individual's array of antigen-specific T cell responses, wherein the amino acid sequence of each fragment characterizes the specificity of each activated T cell clone. Consequently, in some cases, the method is repeated until all polypeptide fragments that are a T cell epitope capable of binding to at least two HLA class I and / or at least two HLA class II of the subject have been identified. This method characterizes the subject's immune response to the polypeptide. The disclosure further provides methods of treating a human subject in need thereof, wherein the method comprises administering to the subject a polypeptide, pharmaceutical composition, or kit of polypeptides from a panel of polypeptides that has been identified or selected by any of the methods above or comprising a fragment of a polypeptide that has been identified or selected by any of the above methods; its use in a method of treating a relevant human subject; and its use in the manufacture of a medicament for treating a relevant subject. Polypeptide fragments that are determined to be immunogenic for a specific human subject according to the above methods can be used to prepare immunogenic compositions specific for a human subject. Accordingly, in another aspect, the disclosure provides methods for designing or preparing a human subject-specific pharmaceutical composition or kit or panel of polypeptides for use in a method of treating a specific human subject, wherein the methods comprise: ( i) selecting a fragment of a polypeptide, where this fragment has been identified as immunogenic for the subject by the above method; (ii) if the fragment selected in step (i) is an HLA class I binding epitope, optionally selecting a longer fragment of the polypeptide, wherein said longer fragment a. comprises the fragment selected in step (i); and b. is a T cell epitope capable of binding to at least three or as many HLA class II molecules as possible from the subject; (iii) selecting a first sequence of up to 50 consecutive amino acids of the polypeptide, where the consecutive amino acids comprise the amino acid sequence of the fragment selected in step (i) or the longest fragment selected in step (ii); (iv) repeating steps (i) to (iii) to select a second amino acid sequence of up to 50 consecutive amino acids from the same polypeptide or a polypeptide different from the first amino acid sequence; (v) optionally further repeating steps (i) to (iii) to select one or more additional amino acid sequences of up to 50 consecutive amino acids from the same polypeptides or polypeptides different from the first and second amino acid sequences; and (vi) designing or preparing a subject-specific pharmaceutical composition, kit, or panel of polypeptides having as active ingredients one or more polypeptides that together have all of the amino acid sequences selected in the preceding steps, optionally wherein one or more or each sequence is flanked at the N- and / or C-terminus by additional amino acids that are not part of the polypeptide sequence. In some cases, each peptide consists of one of the selected amino acid sequences or consists of two or more of the amino acid sequences arranged end-to-end or overlapping in a single peptide. The disclosure further provides a human subject-specific pharmaceutical composition, kit, or panel of polypeptides for use in a method of treating a specific human subject in need thereof, wherein the composition, kit, or panel comprises as active ingredients a first and second peptides and optionally one or more additional peptides, where each peptide comprises an amino acid sequence that is a T cell epitope capable of binding to at least two HLA class I molecules and / or at least two HLA class I molecules. HLA class II of the subject, wherein the amino acid sequence of the T cell epitope of the first, second, and optionally any additional peptides are different from each other, and wherein the pharmaceutical composition or kit optionally comprises at least one diluent, carrier or a pharmaceutically acceptable preservative. The description further provides a pharmaceutical composition specific for a human subject, a kit or a panel of polypeptides for use in a method of treating a specific human subject in need thereof, wherein the composition or kit comprises as active ingredient a polypeptide comprising a first region and a second region and optionally one or more additional regions, wherein each region comprises an amino acid sequence that is a T cell epitope capable of binding to at least two HLA class I molecules and / or at least two HLA class II molecules from the subject, wherein the amino acid sequence of the T cell epitope of the first, second and optionally any additional regions are different from each other, and wherein the pharmaceutical composition or kit optionally comprises at least one pharmaceutically acceptable diluent, carrier or preservative. The disclosure further provides a method for designing or preparing a polypeptide for inducing an immune response in a specific human subject, wherein the method comprises selecting an amino acid sequence that is a T cell epitope capable of binding to at least three HLA molecules of class I or at least three HLA class II molecules from the subject, and designing or preparing a polypeptide comprising the selected amino acid sequence. In other aspects, the disclosure provides a method of inducing an immune response or a method of treatment comprising administering to a human subject in need thereof a pharmaceutical composition specific for a human subject, or the polypeptides, a kit or a panel as described below. described above, wherein the composition, kit, or panel of polypeptides is subject-specific; an immunogenic composition specific for a human subject, the kit or the panel as described above for use in a method of inducing an immune response or a method of treatment of the specific human subject; and the use of a human subject-specific pharmaceutical composition or the polypeptides of a kit or panel as described above in the manufacture of a medicament, wherein the medicament is for inducing an immune response or treating the specific subject. In another aspect, the disclosure provides a system comprising (a) a storage module configured to store data comprising the HLA class I and / or class II genotype of a subject and the amino acid sequence of one or more polypeptides of Test; and (b) a computing module configured to identify and / or quantify amino acid sequences in the test polypeptide(s) that are capable of binding multiple HLA class I molecules from the subject and / or that are capable of binding multiple HLA class II molecules from the subject. The description provides a method of treating a human subject in need thereof, where the method comprises administering to the subject a polypeptide, a panel of polypeptides, a pharmaceutical composition or the polypeptides of the active ingredient of a kit described above, where it has been determined that the subject expresses at least three HLA class I molecules and / or at least three HLA class II molecules capable of binding to the polypeptide or one or more of the polypeptides of the active ingredient of the pharmaceutical composition or kit. 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 disclosure. 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 of <1 PEPI3+ test for diagnostic accuracy determination. Figure 3A Distribution of HLA class I PEPI3+ 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 described peptides for predicting the ensemble of T-cell responses induced by PEPI3+. vaccination of individuals. Figure 3B Distribution of HLA class I PEPI3+ 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: PEPI distribution of HLA class II compared to CD4+ T cell responses measured by a state-of-the-art assay between 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 between 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. HLA class I restricted PEPI3 counts. Light gray: immune responders measured after vaccination in the clinical trial; Dark gray: immune non-responders measured after vaccination in the clinical trial. 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 cluster of HPV vaccine-specific T cell responses from 2 patients. A: 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 defining 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 location of the 1st amino acid 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 ^3 HLA of a patient (PEPI3+). PEPI4 represents peptides that can bind to ^4 HLA of a patient (PEPI4+). PEPI5 represents peptides that can bind to ≥15 HLA of a patient (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 T-cell responses set 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 PEPI3+ score =11 and 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 10A: IPI responder HLA testing. Overall survival (OS) of melanoma patients treated with ipilimumab. Data from 4 independent clinical trials: HLA responders (black line) and HLA non-responders (grey line). Statistical analysis: Cox proportional hazards survival regression. Trial 1: 18 HLA responders and 30 HLA non-responders; Figure 10B: IPI responder HLA testing. Overall survival (OS) of melanoma patients treated with ipilimumab. Data from 4 independent clinical trials: HLA responders (black line) and HLA non-responders (grey line). Statistical analysis: Cox proportional hazards survival regression. Trial 2: 24 HLA responders and 20 HLA non-responders; Figure 10C: HLA testing of the IPI responder. Overall survival (OS) of melanoma patients treated with ipilimumab. Data from 4 independent clinical trials: HLA responders (black line) and HLA non-responders (grey line). Statistical analysis: Cox proportional hazards survival regression. Trial 3: 6 HLA responders and 11 HLA non-responders; Figure 10D: IPI responder HLA testing. Overall survival (OS) of melanoma patients treated with ipilimumab. Data from 4 independent clinical trials: HLA responders (black line) and HLA non-responders (grey line). Statistical analysis: Cox proportional hazards survival regression. Trial 4: 13 HLA responders and 38 HLA non-responders Figure 11 A: Multiple HLA-binding peptides on mutational neoantigens. Correlation of mutational burden, neoantigen burden (neoantigens are neoepitopes according to van Alien). Figure 11B: Multiple HLA-binding peptides on mutational neoantigens. Correlation of PEPI3+ load and clinical benefit (min-Ql-median-Q3-max). Figure 12: HLA map of Rindopepimut on HLA alleles of subjects in the model population. Figure 13: Probability of vaccine antigen expression in tumor cells from patient XYZ. There is a probability of more than 95% 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 14: MRI findings of patient XYZ treated with the personalized vaccine (PIT). This highly pretreated late-stage ovarian cancer patient exhibited an unexpected target response after treatment with the ΡΓΓ vaccine. These MRI findings suggest that the ΡΓΓ vaccine in conjunction with chemotherapy significantly reduced tumor burden. The patient is now continuing treatment with the PIT vaccine. Figure 15: 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). Figure 16: Schematic showing exemplary amino acid positions in overlapping HLA class I and HLA class II binding epitopes in a 30-mer peptide. DESCRIPTION OF THE SEQUENCES SEQ ID NOs 1-13 present the additional peptide sequences described in Table 17. SEQ TD NO: 14-26 present the custom vaccine peptides designed for patient XYZ described in Table 26. SEQ ID NOs: 27-38 present the custom designed vaccine peptides for the ABC patient described in Table 29. SEQ ID NOs: 39-86 present other 9mer T cell epitopes described in Table 33. 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. In some embodiments, the HLA genotype of an individual is obtained or determined by testing a biological sample from the individual. The biological sample typically contains DNA from the subject. The biological sample can be, for example, a blood, serum, plasma, saliva, urine, exhalation, cell, or tissue sample. In some embodiments, the biological sample is a saliva sample. In some embodiments, the biological sample is a buccal sample. An HLA genotype can be obtained or 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. In some embodiments, the HLA genotype is determined using sequence-specific primer (SSP) technologies. In some embodiments, the HLA genotype is determined using sequence-specific oligonucleotide (SSO) technologies. In some embodiments, the HLA genotype is determined using sequence-based typing (SBT) technologies. In some embodiments, the HLA genotype is determined using next generation sequencing. Alternatively, an individual's HLA pool may be stored in a database and accessed using methods known in the art. HLA-epitope binding 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. 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 instances, an epitope, T-cell epitope, polypeptide, polypeptide fragment, or composition comprising a polypeptide or a fragment thereof is "immunogenic" for a specific human subject if it is more likely to induce a specific human response. of T cells or an immune response in the subject that a different T cell epitope (or, in some cases, two different T cell epitopes each) 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 "PEPI" 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 the HLA pool of a specific individual. Unlike an "epitope," PEPIs are individual-specific because different individuals have different HLA molecules that each bind to different T cell epitopes. "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). 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 from an individual, i.e., a fragment identified according to a method described at the moment. "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 I (or II) molecules in 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. "ΡΕΡΙ6" 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 of 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 the purposes of the present description, however, an epitope may be more or less than nine (for HLA class I) or more or less than fifteen (for HLA class II) amino acids in length, so long as the epitope is capable of to bind to 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. Therefore, the present disclosure includes, for example, a method of predicting whether a polypeptide is immunogenic for a specific human subject or identifying a fragment of a polypeptide as immunogenic for a specific human subject, wherein the method comprises the steps of (i ) determine if the polypeptide comprises: a. a sequence of between 7 and 11 consecutive amino acids that is capable of binding to at least two HLA class I of the subject; ob. a sequence of between 13 and 17 consecutive amino acids that is capable of binding to at least two HLA class II of the subject; and (ii) predicting that the polypeptide is immunogenic for the subject if the polypeptide comprises at least one sequence that meets the requirements of step (i); predicting that the polypeptide is not immunogenic for the subject if the polypeptide does not comprise at least one sequence that meets the requirements of step (i); or identifying said consecutive sequence of amino acids as the sequence of a fragment of the polypeptide that is immunogenic for the subject. 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. As provided herein, a presentation of T cell epitopes by multiple HLAs from an individual is generally needed to activate a T cell response. Accordingly, the methods of the invention comprise determining whether a polypeptide has a sequence that is a T cell epitope capable of binding to at least two HLA class I molecules or at least two HLA class II (PEPI2+) molecules from a specific human subject. The best predictor of a cytotoxic T cell response to a given polypeptide is the presence of at least one T cell epitope presented by three or more HLA class I molecules from an individual (<1 PEPI3+). Accordingly, in some instances the method comprises determining whether a polypeptide has a sequence that is a T cell epitope capable of binding three HLA class I molecules from a specific human subject. In some cases, the method comprises determining whether a polypeptide has a sequence that is a T cell epitope capable of binding to only three HLA class I from a specific human subject. A T helper cell response can be predicted by the presence of at least one T cell epitope presented by three or more (<1 PEPI3+) or 4 or more (<1 PEPI4+) HLA class II in an individual. Thus, in some instances, the method comprises determining whether a polypeptide has a sequence that is a T cell epitope capable of binding to three class II HLAs from a specific human subject. In other cases, the method comprises determining whether a polypeptide has a sequence that is a T-cell epitope capable of binding to at least four class II HLAs from a specific human subject. In other cases, the method comprises determining whether a polypeptide has a sequence that is a T cell epitope capable of binding only three and / or only four class II HLAs from a specific human subject. In some instances, the disclosure can be used to predict whether a polypeptide / fragment will induce a cytotoxic T cell response and a helper T cell response in a specific human subject. The polypeptide / fragment comprises an amino acid sequence that is a T cell epitope capable of binding to multiple HLA class I molecules from the subject and an amino acid sequence that is a T cell epitope capable of binding to multiple HLA class I molecules from the subject. class II of the subject. HLA class I binding and HLA class II binding epitopes may completely or partially overlap. In some cases, such fragments of a polypeptide can be identified by screening for an amino acid sequence that is a T cell epitope capable of binding in multiples (eg, at least two or at least three) HLA class I molecules from the subject, and then analysis of one or more longer fragments of the polypeptide that extend at the N- and / or C-terminus to bind to one or more HLA class II molecules from the subject. subject. 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". polypeptide antigens Described herein are methods for predicting whether a polypeptide is immunogenic for a specific human subject and for identifying a fragment of a polypeptide as immunogenic for a specific human subject. 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, or 50 amino acids. The terms "fragment" or "fragment of a polypeptide", as used herein, refer to an amino acid chain or amino acid sequence typically of reduced length relative to the reference polypeptide or a reference polypeptide and which 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 polypeptide is or the polypeptide consists of all or part of an antigen that is expressed by a pathogenic organism (for example, a bacterium or parasite), a virus, or a cancer cell, that is associated with a response or autoimmune disorder or a cell associated disease, or that is an allergen or an ingredient of a drug or pharmaceutical composition, such as an immunotherapy composition or vaccine. In some instances, the method of the disclosure comprises an initial step of identifying or selecting a suitable polypeptide, eg, a polypeptide as described further below. The polypeptide or antigen may be expressed in the cells or specifically in diseased cells of the subject (eg, a tumor-associated antigen, a polypeptide expressed by an intracellular virus, parasite, or bacteria, or the in vivo product of an immunotherapy composition or vaccine) or acquired from the environment (eg, a food, an allergen, or a drug). The polypeptide or antigen may be present in a sample taken from the specific human subject. HLA and polypeptide antigens can be precisely defined by nucleotide or amino acid sequences and sequenced using methods known in the art. The polypeptide or antigen may be a cancer or tumor associated antigen (TAA). TAAs are proteins expressed in cancer or tumor cells. The cancer or tumor cell may be present in a sample obtained from the subject. Examples of TAAs include novel antigens (neoantigens) expressed during tumorigenesis, products of oncogenes and tumor suppressor genes, overexpressed or aberrantly expressed cellular proteins (eg, HER2, MUC1), antigens produced by oncogenic viruses (eg. , EBV, HPV, HCV, HBV, HTLV), testicular cancer antigens (CTA)(eg, MAGE family, NY-ESO), and cell type-specific differentiation antigens (eg, MART- 1). TAA sequences can be found experimentally, in published scientific articles, or through publicly available databases, such as the Ludwig Institute for Cancer Research database (www.cta.lncc.br / ), the Immunity Database to cancer (cancerimmunity.org / peptide / ) and the TANTIGEN tumor T cell antigen database (cvc.dfci.harvard.edu / tadb / ). In some cases, the polypeptide or antigen is not expressed or is minimally expressed in normal healthy cells and tissues, but is expressed (in those cells or tissues) in a high proportion of (with a high frequency in) subjects having a disease or particular condition, such as a type of cancer or a cancer derived from a particular tissue or cell type, for example, breast cancer, ovarian cancer, or melanoma. An additional example is colorectal cancer. Other non-limiting examples of cancer include non-melanoma skin cancer, lung cancer, prostate cancer, kidney cancer, bladder cancer, stomach cancer, liver cancer, cervical cancer, esophagus cancer, non-Hodgkin's lymphoma, leukemia, pancreatic cancer, uterine, lip, oral cavity, thyroid, brain, nervous system, gallbladder, larynx, pharynx, myeloma, nasopharyngeal cancer, Hodgkin's lymphoma, testicular cancer, and Kaposi's sarcoma. Alternatively, the polypeptide may be expressed at low levels in normal healthy cells, but at high levels (overexpressed) in diseased (eg, cancer) cells or in subjects having the disease or condition. In some cases, the polypeptide is expressed at, or expressed at, a high level relative to normal healthy subjects or cells in at least 2%, 5%, 10%, 15%, 20%, 25 %, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or more of such individuals, or of a human subpopulation corresponding to the subject. For example, the subpopulation may be matched to the subject by ethnicity, geographic location, gender, age, disease, stage or type of disease, genotype, or expression of one or more biomarkers. In some cases, expression frequencies can be determined from scientific literature and published figures. In some cases, the method of the description comprises a step of identification or selection of said polypeptide. In some cases, the polypeptide is associated with or highly (over)expressed in cancer cells or solid tumors. Exemplary cancers include carcinomas, sarcomas, lymphomas, leukemias, germ cell tumors, or blastomas. The cancer may or may not be a hormone-dependent or hormone-related cancer (eg, an estrogen- or androgen-related cancer). The tumor can be malignant or benign. The cancer may or may not be metastatic. In some cases, the polypeptide is a testicular cancer antigen (CTA). 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. CTA 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 polypeptide may be a mutational neoantigen, which is expressed by a cell, eg, a cancer cell, of the individual, but altered from the analogous protein in a normal or healthy cell. In some instances, the methods of the disclosure comprise the step of identifying a polypeptide that is a mutational neoantigen or that is a mutational neoantigen in the specific human subject, or of identifying a neoepitope. For example, cl neoantigen may be present in a sample obtained from the subject. Mutational neoepitopes or neoantigens can be used to target disease-associated cells, eg, cancer cells, that express the neoantigen or a neoantigen comprising the neoepitope. Mutations in a polypeptide expressed by a cell, eg, a cell in a sample taken from a subject, can be detected, for example, by sequencing, but most do not induce an immune response against cells expressing neoantigens. Currently, the identification of mutational neoantigens that do induce an immune response is based on the prediction of HLA-restricted mutational epitopes and also the in vitro evaluation of the immunogenicity of the predicted epitopes in the individual's blood sample. This process is inaccurate, long and expensive. As provided herein, the identification of mutational epitopes (neoepitopes) that bind to multiple HLA molecules reproducibly defines the immunogenicity of mutational neoantigens. Thus, in some instances according to the disclosure, the polypeptide is a mutational neoantigen and the immunogenic fragment of the polypeptide comprises a neoantigen-specific mutation (or consists of a neoepitope). The polypeptide may be an intracellularly expressed viral protein. Examples include HPV16 E6, E7; HIV Tat, Rev, Gag, Pol, Env; HTLV-Tax, Rex, Gag, Env, human herpes virus proteins, dengue virus proteins. The polypeptide may be an intracellularly expressed parasite protein, eg malarial proteins. The polypeptide may be an active ingredient of a pharmaceutical composition, such as a vaccine or immunotherapy composition, optionally a candidate active ingredient for a novel pharmaceutical composition. 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. In other cases, the polypeptide may be a target polypeptide antigen of a pharmaceutical composition, a vaccine, or immunotherapy. A polypeptide is a target polypeptide antigen if the composition is designed to induce an immune response (eg, a cytotoxic T-lymphocyte response) that is directed at the polypeptide. A target polypeptide antigen is typically a polypeptide that is expressed by a pathogenic organism, a virus, or a diseased cell such as a cancer cell. A target polypeptide antigen may be a TAA or a CTA. Currently, >200 clinical trials are investigating cancer vaccines with tumor antigens. The polypeptide may be an allergen that enters an individual's body, for example, via the skin, lungs, or oral routes. Some non-limiting examples of suitable polypeptides include those listed in one or more of Tables 2 to 7. Genetic sequences can be obtained by sequencing biological materials. Sequencing can be performed by any suitable method that determines DNA and / or RNA and / or amino acid sequences. The description uses HLA genotypes and amino acid sequences. However, methods for identifying the HLA genotype of an individual's genetic sequences and methods for obtaining amino acid sequences derived from DNA or RNA sequence data are not the subject of the disclosure. <£ C C 4S σ Prediction of an individual's immune response to a polypeptide antigen Specific polypeptide antigens induce immune responses in only a fraction of human subjects. Currently, there is no diagnostic test that can predict whether a polypeptide antigen is likely to induce an immune response in an individual. In particular, there is a need for a test that can predict whether a person is an immune responder to an immunotherapy or vaccine composition. According to the present disclosure, an individual's polypeptide antigen-specific T cell response is defined by the presence within the polypeptide of one or more fragments that can be presented via multiple HLA class I molecules or multiple HLA class I molecules. IT class HLA of the individual. In some instances, the disclosure provides a method of predicting whether a subject will have an immune response to administration of a polypeptide, wherein an immune response is predicted if the polypeptide is immunogenic according to any method described herein. A cytotoxic T cell response is predicted if the polypeptide comprises at least one amino acid sequence that is a T cell epitope capable of binding to at least two HLA class I molecules from the subject. A T helper cell response is predicted if the polypeptide comprises at least one amino acid sequence that is a T cell epitope capable of binding to at least two HLA class II molecules from the subject. No cytotoxic T cell response is predicted if the polypeptide does not comprise any amino acid sequence that is a T cell epitope capable of binding to at least two HLA class I molecules from the subject. No helper T cell response is predicted if the polypeptide does not comprise any amino acid sequence that is a T cell epitope capable of binding to at least two HLA class II molecules from the subject. In some cases, the polypeptide is an active component of a pharmaceutical composition, and the method comprises predicting the development or production of anti-drug antibodies (ADA) to the polypeptide. The pharmaceutical composition may be a drug selected from those listed in Table 8. According to the present description, the development of ADA will occur if, or to the extent that, an active component polypeptide is recognized by multiple HLA molecules. class II from the subject, generating a T helper cell response to support an antibody response to the active ingredient. The presence of said epitopes (PEPT) can predict the development of ADA in the subject. The method may further comprise selecting or recommending for treatment of the specific human subject administering to the subject a pharmaceutical composition predicted to induce little or no ADA, and optionally further administering the composition to the subject. In other cases, the method predicts that the pharmaceutical composition will induce unacceptable ADA, and the method further comprises selecting, recommending, or treating the subject with a different treatment or therapy. The polypeptide may be a checkpoint inhibitor. The method may comprise predicting whether the subject will respond to treatment with the checkpoint inhibitor. Table 8 - Exemplary drugs associated with ADA-related adverse events There is also currently no test that can predict the likelihood that a person will have a clinical response to, or derive clinical benefit from, an immunotherapy or vaccine composition. This is important because currently measured T cell responses in a cohort of individuals participating in immunotherapy or vaccine clinical trials correlate poorly with clinical responses. That is, the clinical responder subpopulation is substantially smaller than the immune responder subpopulation. Therefore, to allow for the personalization of vaccines and immunotherapies, it is important to predict not only the likelihood of an immune response in a specific subject, but also whether the drug-induced immune response will be clinically effective (eg, whether it can destroy cancer cells, cells infected with pathogens or pathogens). The inventors discovered that 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 PEPI3+) predicts a clinical response. In other words, if <2 PEPI3+ can be identified within the active ingredient polypeptides of a composition of immunotherapy or vaccine, an individual is likely to be a clinical responder. 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. Therefore, in some cases the disclosure provides a method of predicting whether the subject will have a clinical response to the administration of a pharmaceutical composition such as an immunotherapy or vaccine composition comprising one or more polypeptides as active ingredients. The method may comprise determining whether the polypeptide(s) together comprise at least two different sequences, each of which is a T cell epitope capable of binding to at least two, or in some cases at least three, HLA-class molecules. I of the subject; and predicting that the subject will have a clinical response to administration of the pharmaceutical composition if the polypeptide(s) together comprise at least two different sequences, each of which is a T cell epitope capable of binding to at least two, or in some cases three, HLA class I molecules from the subject; or that the subject will not have a clinical response to administration of the pharmaceutical composition if the polypeptide(s) together do not comprise more than one sequence that is a T cell epitope capable of binding to at least two, or in some cases three, molecules of HLA class I of the subject. For the purposes of this method, two T cell epitopes are "different" from each other if they have different sequences, and in some cases also if they have the same repeating sequence in a target polypeptide antigen. In some cases, different T cell epitopes on a target polypeptide antigen do not overlap with each other. In some cases, all fragments of one or more polypeptides or polypeptides of the active ingredient that are immunogenic for a specific human subject are identified using the methods described herein. Identification of at least one fragment of the polypeptides that is a T cell epitope capable of binding to at least two or at least three HLA class I molecules from the subject predicts that the polypeptides will or is likely to elicit a T cell response. T cytotoxic in the subject. Identification of at least one fragment of the polypeptides that is a T-cell epitope capable of binding to at least two, at least three, or at least four HLA class II molecules from the subject predicts that the polypeptides will or is likely to cause a T helper cell response in the subject. Identification of any fragment of the polypeptides that is a T-cell epitope capable of binding to at least two or at least three HLA class I molecules from the subject predicts that the polypeptides will not or likely will not elicit a T cell response. T cytotoxic in the subject. Identification of any fragment of the polypeptides that is a T-cell epitope capable of binding to at least two, at least three, or at least four HLA class II molecules from the subject predicts that the polypeptides will not or likely will not cause a T helper cell response in the subject. The identification of at least two fragments of one or more polypeptides of the active ingredient of an immunotherapy or vaccine composition, where each fragment is a T cell epitope capable of binding to at least two or at least three HLA class I molecules of the subject predicts that the subject is more likely to have, or will have, a clinical response the composition. Identification of fewer than two fragments of one or more polypeptides that are T cell epitopes capable of binding to at least two or at least three HLA class I molecules from the subject predicts that the subject is less likely to have, or will not have, , a clinical response to the composition. Without wishing to be bound by theory, 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 cancer or tumor cells or cells infected by viruses or pathogens such as HTV, are usually heterogeneous both within and between 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. In addition, 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. The probability that a subject will respond to treatment is therefore 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) the (over)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. 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 invention comprises a step of determining the frequency of expression of a relevant target polypeptide antigen in a relevant population. A series of pharmacodynamic biomarkers are described to predict the activity / effect of vaccines in individual human subjects as well as in populations of human subjects. The biomarkers were developed specifically for cancer vaccines, but similar biomarkers can be used for other immunotherapy compositions or vaccines. 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 on PEPT-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, cl AGP50 will be 0. In general, cl 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 vaccinia antigens in e.g. eg, the tumor 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). The results of a prediction as stated above can be used to inform a physician's decisions regarding treatment of the subject. Therefore, in some cases the polypeptide is an active ingredient, for example, of a vaccine or immunotherapy composition, the method of the disclosure predicts that the subject will have, is likely to have, or has a minimal probability above a threshold of having an immune response and / or a clinical response to a treatment comprising administering the active ingredient polypeptide to the subject, and the method further comprises selecting the treatment or selecting the immunotherapy or vaccine composition for treatment of the specific human subject. Also provided is a method of treatment with a subject-specific pharmaceutical composition, kit, or polypeptide panel comprising one or more polypeptides as active ingredients, wherein the pharmaceutical composition, kit, or polypeptide panel has been determined to have a likely minimum threshold of inducing a clinical response in the subject, wherein the probability of response was determined using a method described herein. In some cases, the trough threshold is defined by one or more of the pharmacodynamic biomarkers described herein, for example, a trough PEPI3+ count (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 or more PEPT3+), a minimum AGP count (for example, AGP = at least 2 or at least 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 or more), and / or a minimum mAGP (eg, AGP = at least 2 or at least 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 or more). For example, in some cases a subject is selected for treatment if his or her probability of a response directed to a predefined number of target polypeptide antigens, optionally where target polypeptide antigens are (predicted) to be expressed, is greater than a predetermined threshold (eg, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 or more). Alternatively, the method may predict that the polypeptide(s) in the composition will not elicit a T cell response and / or a clinical response in the subject and further comprises selecting a different treatment for the specific human subject. Prediction of an autoimmune or toxic immune response to a polypeptide antigen Differences between HLAs can influence the likelihood of developing a disease, condition, or autoimmune response. In some instances, the method of the disclosure can be used to identify a polypeptide or polypeptide fragment that is immunogenic and / or associated with an autoimmune disorder or response. In some cases, the method comprises determining whether a polypeptide comprises an amino acid sequence that is a T cell epitope capable of binding to at least three, at least four, or at least five HLA class I from a subject; or in other cases, a sequence that is a T cell epitope capable of binding to at least four, at least five, or at least six HLA class II from a subject; and identifying the polypeptide or said sequence as immunogenic or as related to or associated with an autoimmune disorder or autoimmune response in the subject. Differences between HLAs may also influence the likelihood that a subject will experience immune toxicity from a drug or polypeptide administered to the subject. A toxic immune response may be present if a polypeptide administered to the subject comprises a fragment that corresponds to a fragment of an antigen expressed on normal healthy cells of the subject and that comprises an amino acid that is a T cell epitope capable of binding to multiple HLA molecules. of class I of the subject. Thus, in some instances according to the disclosure, the method is used to identify a toxic immunogenic region or fragment of a polypeptide or to identify subjects that may experience immune toxicity in response to administration of one or more polypeptides or polypeptide fragments. these. The polypeptide can be an active ingredient of a vaccine or immunotherapy composition. The method may comprise determining whether the polypeptides comprise a sequence that is a T cell epitope capable of binding to at least two, or in other cases at least three, HLA class I molecules from the subject. In some cases, the method comprises determining that the polypeptide comprises a sequence that is a T cell epitope capable of binding to at least four or at least five HLA class I molecules from the subject; or an amino acid sequence that is a T cell epitope capable of binding to at least four, at least five, at least six, or at least seven class II HLAs from the subject. The method may further comprise identifying said sequence as immunogenic toxic to the subject or predicting a toxic immune response in the subject. In other cases, none of said amino acid sequences are identified and the method further comprises predicting any toxic immune response in the subject. The method may further comprise selecting or recommending for treatment of the subject the administration of one or more polypeptides or a pharmaceutical composition that is predicted to induce little or no immune toxicity, and optionally further treating the subject by administering the polypeptide. The disclosure also provides a method of treating a subject in need thereof by administering said polypeptide or composition to the subject. In some instances, a method described herein further comprises mutating a polypeptide predicted to be immunogenic for a specific human subject, or predicted to be immunogenic in a proportion of subjects in a human population. Also provided is a method of reducing the immunogenicity of a polypeptide that has been identified as immunogenic in a specific human subject or in a proportion of a human population using any of the methods described herein. The polypeptide can be mutated to reduce the amount of PEPI in the polypeptide or to reduce the amount of HLA class I or class II molecules from the subject or said population that bind to the fragment of the polypeptide identified as being immunogenic in the subject or in a proportion of that population. In some cases, the mutation may reduce or prevent a toxic immune response or may increase efficacy by preventing the development of ADA in the subject or in a proportion of that population. The mutated polypeptide may further be selected or recommended for treatment of the subject or a subject of said population. The subject may be further treated by administration of the mutated polypeptide. The disclosure also provides a method of treating a subject in need thereof by administering said mutated polypeptide to the subject. Predicting an Individual's Response to Checkpoint Inhibitor Treatment Normally, some or all of the tumor-induced clones of tumor-specific T cells are inactive or poorly functional in patients with metastatic cancer. Dormant tumor-specific T cells cannot kill tumor cells. A fraction of these dormant T cells can be reactivated by checkpoint inhibitors (such as Ipilimumab), for example, monoclonal antibodies that recognize checkpoint molecules (eg, CTLA-4, PD-1, Lag- 3, Tim-3, TIGIT, BTLA). In accordance with the present disclosure, treating a subject with a checkpoint inhibitor will only be effective if or to the extent that the expressed cancer antigens can be adequately recognized by the individual's HLA, i.e., whether there are epitopes on the cancer- or disease-associated antigens that are recognized by multiple, preferably at least three, HLA class I molecules from the subject. Therefore, in some cases the methods of the disclosure can be used to identify one or more or subset of T cell clones that can be reactivated through a checkpoint inhibitor or to predict potential responders to immunotherapies. with checkpoint inhibitors. Accordingly, in some instances the disclosure provides a method of predicting whether a subject will respond to cancer with a checkpoint inhibitor. In some cases, the method comprises the step of identifying or selecting one or more polypeptides or polypeptide fragments that are associated with the disease or condition to be treated or that are associated with achieving an immune or clinical response to treatment with an inhibitor. checkpoints. In some cases, the polypeptide is a tumor-associated and / or mutational antigen. The polypeptide may be present in a sample obtained from the subject. The polypeptide may be a polypeptide frequently (over)expressed in a population corresponding to the subject and / or the disease. The polypeptide may consist of or comprise a PEPI (or PEPI3+) identified in a subject known to have responded positively to one or the checkpoint inhibitor. The polypeptide may comprise or consist of an amino acid sequence that is stored, recorded, or retrieved from a database. In some cases, the method comprises determining whether the polypeptides comprise a sequence that is a T cell epitope capable of binding to multiple HLA class I molecules from the subject. In some cases, the presence of at least two or at least three, four, five, six, seven or eight of said different amino acid sequences, and / or the presence of said amino acid sequences in at least two or at least three, four or five different target polypeptide antigens. In some cases, the method comprises determining whether the polypeptides comprise a sequence that is a T cell epitope capable of binding to at least two, or in some cases at least three or at least four, HLA class II molecules from the subject. A response to treatment with the or a checkpoint inhibitor can be predicted if the above requirements are met. No response or clinical response can be predicted if the above requirements are not met. The disclosure also provides a method for identifying a fragment of a polypeptide or a T cell epitope in a polypeptide that may be targeted by the subject's immune response after treatment with a checkpoint inhibitor, or that will be targeted by T cells. T that are reactivated through treatment with a checkpoint inhibitor. The method may further comprise selecting, recommending, and / or administering a checkpoint inhibitor to a subject predicted to respond, or selecting, recommending, and / or administering a different treatment to a subject predicted to be unresponsive to an inhibitor. of control points. In other instances, the disclosure provides a method of treating a human subject in need thereof, wherein the method comprises administering a checkpoint inhibitor to the subject, wherein the subject is predicted to respond to administration of a checkpoint inhibitor. control via the method described herein. Checkpoint inhibitors include, but are not limited to, PD-1 inhibitors, PD-LL inhibitors, Lag-3 inhibitors, Tim-3 inhibitors, TIGIT inhibitors, BTLA inhibitors, and CTLA-4 inhibitors, for example. example. Costimulatory antibodies deliver positive signals through immunoregulatory receptors including, but not limited to, ICOS, CD137, CD27 OX-40, and GITR. In one embodiment, the checkpoint inhibitor is a CTLA-4 inhibitor. Design and preparation of pharmaceutical compositions for an individual human subject In some aspects, the disclosure provides a method of designing or preparing a polypeptide, or a polynucleic acid encoding a polypeptide, for inducing an immune response, cytotoxic T-lymphocyte response, or helper T-lymphocyte response in a specific human subject. . The description also provides a drug, immunogenic composition or pharmaceutical composition specific for a human subject, a kit or panel of peptides, methods of designing and preparing the same, compositions obtainable by these methods and their use in a method of inducing an immune response, cytotoxic T-lymphocyte response, or helper T-lymphocyte response in the subject, or a method of treating, vaccinating, or providing immunotherapy to the subject. The pharmaceutical composition, kit or panel of peptides has as active ingredients one or more polypeptides, which together comprise two or more epitopes of T lymphocytes (PEPI) capable of binding multiple HLA class I molecules or multiple HLA class II molecules. of the subject, that are immunogenic to the subject as described herein, or that were identified as immunogenic to the subject by a method described herein. 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. Typically, each PEPI is a fragment of a target polypeptide antigen, and polypeptides comprising one or more of the PEPIs are the target polypeptide antigens for treatment, vaccination, or immunotherapy. The method may comprise the step of identifying one or more suitable target polypeptide antigens. Typically, each target polypeptide antigen will be associated with the same disease or condition, pathogenic organism, group of pathogenic organisms, virus, or type of cancer. The composition, kit or panel may comprise or the method may comprise selecting for each PEPI a sequence of up to 50, 45, 40, 35, 30, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12 , 11, 10 or 9 consecutive amino acids of the target polypeptide antigen, such as a polypeptide described herein, where these consecutive amino acids comprise the amino acid sequence of PEPI. 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 consecutive sequence of 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 neo-epitopes 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 functional amino acid sequences. Neoepitopes can induce unwanted T cell responses against healthy cells (autoimmunity). The peptides can be designed, or the peptides can be tested, to avoid or eliminate 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 to 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. The methods of the disclosure can be used to identify or analyze such neoepitopes as described herein. Alignment can be determined using known methods, such as BLAST algorithms. Software for performing BLAST analyzes is publicly available through the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). The at least two multi-HLA binding PEPIs of the polypeptides of the composition may target a single antigen (eg, a polypeptide vaccine comprising two multi-HLA binding PEPIs derived from a single antigen, e.g., a tumor-associated antigen, vaccine / immunotherapy target) or may target different antigens (eg, a polypeptide vaccine comprising a multi-HLA-binding PEPI derived from an antigen, eg, an antigen tumor-associated antigen, and a second multi-HLA binding PEPI derived from a different antigen, eg, a different tumor-associated antigen, both targets of the vaccine / immunotherapy). In some cases, the active ingredient polypeptides together comprise, or the method comprises, a total of or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 , 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 or more different PEPIs. PEPIs may be fragments of one or more other target polypeptide antigens. By identifying specific fragments of each target polypeptide antigen that are immunogenic for a specific subject, it is possible to incorporate multiple such fragments, optionally from multiple different target polypeptide antigens, into a single active ingredient polypeptide or multiple active ingredient polypeptides intended to their use in combination or to maximize the number of clones of T cells that can be activated by one or more polypeptides of a given length. Currently, most immunotherapy and vaccine compositions target only a single polypeptide antigen. However, in accordance with the present disclosure, in some cases it is beneficial to provide a pharmaceutical composition or polypeptide of the active ingredient targeted to 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 PEPIs in a single treatment (administration of one or more pharmaceutical compositions that together comprise multiple PEPIs) can be illustrated by the personalized vaccine polypeptides described in Examples 17 and 18 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 the 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 mAGP 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 17 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 in 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 18 contains an additional 8 PEPIs and therefore the probability of having a mAGP is greater than 99.93%. Accordingly, in some cases the PEPIs of the active ingredient polypeptides are from two or more different target polypeptide antigens, eg, different antigens associated with a specific disease or condition, eg, different cancer or tumor-associated antigens or antigens. expressed by a target pathogen. In some cases, the PEPTs are of a total of or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 or more different target polypeptide antigens. The different target polypeptide antigens can be any different polypeptides that are useful to target or can be selectively addressed with different PEPI3+. In some cases, the different target polypeptide antigens are non-homologous or non-paralogous or have less than 95%, 90%, 85%, 80%, 75%, 70%, 60%, or 50% sequence identity throughout the full length of each polypeptide. In some cases, the different polypeptides are those that do not share any PEPI3+. Alternatively, in some cases the PEPI3+ are from different target polypeptide antigens when they are not shared with other polypeptide antigens that are targeted by the active ingredient polypeptides. In some cases, one or more or each of the immunogenic polypeptide fragments is from a polypeptide that is present in a sample taken from the specific human subject. This indicates that the polypeptide is expressed in the subject, eg, a cancer or tumor associated antigen or a cancer / testis antigen expressed by cancer cells of the subject. In some cases, one or more or each of the polypeptides is a mutational neoantigen or an expression neoantigen of the subject. One or more or each fragment may comprise a neoantigen-specific mutation. Because mutational neoantigens are subject-specific, a composition that targets one or more specific neoantigen mutations is personalized with respect to your specific disease and your specific HLA set. In other cases, one or more or each of the immunogenic polypeptide fragments is from a target polypeptide antigen that is generally not expressed or minimally expressed in normal healthy tissue or cells, but is expressed in a high proportion of (with a high frequency in) subjects or in the diseased cells of a subject having a particular disease or condition, as described above. The method may comprise identifying or selecting said target polypeptide antigen. In some cases, two or more or each of the PEPI / immunogenic polypeptide fragments are from different cancer- or tumor-associated antigens, where each of these is (over)expressed at a high frequency in subjects having one type of cancer. or a cancer derived from a particular tissue or cell type. In some cases, the immunogenic polypeptide fragments are from a total of or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 cancer-associated polypeptides or different tumor. In some cases, one or more, each or at least one, at least two, at least three, at least four, at least five, at least six or at least seven of the polypeptides are selected from the antigens listed in any of the tables from 2 to 7. In some cases, one or more or each of the target polypeptide antigens is a testicular cancer antigen (CTA). In some cases, the PEPI / immunogenic polypeptide fragments are at least 1, at least 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 CTAs, of a total of 3 or more different target polypeptide antigens, where optionally 1, 2 or all three or at least three are CTAs, of 4 or more different polypeptide antigens, where optionally 1, 2, 3 or all four or at least 1, 2, 3 or 4 are CTA, from 5 or more different polypeptide antigens, where optionally 1, 2, 3, 4 or all five or at least 1, 2, 3, 4 or 5 are CTAs, from 6 or more different polypeptide antigens, wherein optionally 1, 2, 3, 4, 5 or all six or at least 1, 2, 3, 4, 5 or 6 are CTAs, from 7 or more different polypeptide antigens, where optionally 1, 2, 3, 4, 5, 6 or all 7 or at least 1, 2, 3, 4, 5, 6 or 7 are CTA, or from 8 or more different polypeptide antigens, wherein optionally 1, 2, 3, 4, 5, 6, 7 or all 8 or at least 1, 2, 3, 4, 5, 6, 7 or 8 They are CTAs. In some cases, one or more or each of the target polypeptide antigens is expressed by a bacterium, a virus or a parasite. In some cases, one or more of the polypeptide fragments comprise an amino acid sequence that is a T cell epitope capable of binding to at least two or at least three HLA class I of the subject, and one or more of the fragments of polypeptide comprises an amino acid sequence that is a T cell epitope capable of binding to at least two, at least three or at least four class II HLAs of the subject, wherein binding fragments to HLA class I and HLA class II can optionally overlap. A composition prepared by such a method can elicit a cytotoxic T-lymphocyte response and a helper T-lymphocyte response in the specific human subject. Immunogenic and 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 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, e.g. g., 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 person 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 added 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 Freund (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 Montanidc ISA-51 (Scppic, 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, peptides, 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 PEPIs under suitable sterile conditions according to known techniques to produce the final product. Examples of suitable polypeptide fragment compositions 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 Vaccinc 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 Sp6, 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 normally 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 techniques and protocols mentioned above 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 may be administered together / 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. Multiple PEPI pharmaceutical compositions, 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. One skilled in the art will recognize that 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, eg 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 / checkpoint inhibitor therapy, costimulatory antibodies, cytotoxic or non-cytotoxic 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 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; ctylcnimines / mctylmcamines such as hcxamctylmcamine, thiotepa; alkyl sulfonates such as busulfan; antimetabolites including folic acid analogs such as methotrexate (ametopterin); alkylating agents, antimetabolites, pyrimidine analogs 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 IFNα, 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 procarbazine (N-methylhydrazine, MIH) and procarbazine; adrenocortical suppressants such as mitotane (ο,ρ'-DDD) and amino glutethimide; taxol and analogous s / derivatives; hormones / hormone therapy 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 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 an HLA class I. In another specific embodiment, immunotherapy comprises the administration of one or more plus PEPI to an individual to elicit a cytotoxic T cell response against cells presenting tumor-associated antigens (TAAs) or cancer-associated antigens (CTAs) 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. 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 blastomas. The cancer may or may not be a hormone-dependent or hormone-related cancer (eg, an estrogen- or androgen-related cancer). In other cases, the description refers to the treatment of a viral, bacterial, fungal or parasitic infection, or any other disease or condition that can be treated with immunotherapy. Systems The description provides a system comprising a storage module configured to store data comprising the HLA class I and / or class II genotype of a subject and the amino acid sequence of one or more test polypeptides; and a computing module configured to identify and / or quantify amino acid sequences in the test polypeptide(s) that are capable of binding multiple HLAs from the subject. The system may be for obtaining data from at least one sample from at least one subject. The system may comprise an HLA genotyping module for determining the HLA class I and / or class II genotype of a subject. The storage module may be configured to store the data output of the genotyping module. The HLA genotyping module can receive a biological sample obtained from the subject and determines the HLA class I and / or class II genotype of the subject. The sample typically contains DNA from the subject. The sample can be, for example, a blood, serum, plasma, saliva, urine, exhalation, cell, or tissue sample. The system may further comprise an output module configured to display the sequence of one or more fragments of the one or more polypeptides predicted to be immunogenic for the subject, any output prediction or treatment selection or recommendation described herein or the value of any pharmacodynamic biomarker described herein. Additional Modalities of Description 1. A human subject-specific pharmaceutical composition for the treatment of a disease or disorder in a specific human subject comprising (a) at least two different polypeptides, wherein each of the at least two different polypeptides is 10-50 amino acids in length and comprises a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three HLA class II molecules from the subject, and wherein the epitope of T cells of each of the at least two polypeptides are different from each other; and (b) a pharmaceutically acceptable adjuvant. 2. The specific pharmaceutical composition for a human subject of item 1 comprising at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 or at least 12 different polypeptides.3. The specific pharmaceutical composition for a human subject of item 1 comprising 3-40 different polypeptides.4. The specific pharmaceutical composition for a human subject of item 1, wherein the T-lymphocyte epitope that binds to at least three HLA class I molecules of the subject comprises between 7 and 11 amino acids, and / or the T-lymphocyte epitope that binds to at least three HLA class II molecules comprises between 13 and 17 amino acids.5. The specific pharmaceutical composition for a human subject of item 1, where the epitopes of the at least two different polypeptides are from a single antigen.6. The specific pharmaceutical composition for a human subject of item 1, where the epitopes of the at least two different polypeptides are from two or more different antigens.7. The specific pharmaceutical composition for a human subject of item 5, where the antigen is an antigen expressed by a cancer cell, a neoantigen expressed by a cancer cell, a cancer-associated antigen, a tumor-associated antigen, or an antigen expressed by a target pathogenic organism, an antigen expressed by a virus, an antigen expressed by a bacterium, an antigen expressed by a fungus, an antigen associated with an autoimmune disorder, or is an allergen.8. The specific pharmaceutical composition for a human subject of item 7, where the cancer cell is from the subject. 9. The specific pharmaceutical composition for a human subject of item 5, wherein the antigen is selected from the antigens listed in tables 2 to 7.10. The specific pharmaceutical composition for a human subject of item 1, wherein the at least two different polypeptides also comprise up to 10 amino acids that flank the epitope of T lymphocytes that are part of a consecutive sequence that flanks the epitope in a corresponding antigen.11. The specific pharmaceutical composition for a human subject of item 1, where the at least two different polypeptides also comprise up to 10 amino acids that flank the epitope of T lymphocytes that are not part of a consecutive sequence that flanks the epitope in a corresponding antigen.12 . The specific pharmaceutical composition for a human subject of item 1, wherein two of the at least two polypeptides are arranged end-to-end or overlap in a bound polypeptide.13. The specific pharmaceutical composition for a human subject of item 12 comprising two or more different bound polypeptides, wherein the two or more different bound polypeptides comprise different epitopes from each other.14. The specific pharmaceutical composition for a human subject of item 13, wherein the bound polypeptides have been analyzed to eliminate substantially all neoepitopes that span a junction between the two polypeptides and that (i) corresponds to a fragment of a human polypeptide expressed in cells healthy from the subject; (ii) is a T cell epitope capable of binding to at least two HLA class I molecules from the subject; or(iii) meets the requirements (i) and (ii). 15. The specific pharmaceutical composition for a human subject of item 1, wherein the at least two polypeptides do not comprise any amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and cs an epitope of T lymphocytes capable of binding to at least two HLA class I molecules of the subject. 16.The specific pharmaceutical composition for a human subject of item 1 that further comprises a pharmaceutically acceptable diluent, carrier, preservative or a combination of these. 17. The specific pharmaceutical composition for a human subject of item 1, wherein 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.18. A kit comprising one or more separate containers, each container comprising: (i) one or more polypeptides that are 10-50 amino acids in length that comprise an amino acid sequence that is a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three HLA class II molecules from the subject; and (ii) a pharmaceutically acceptable adjuvant, diluent, carrier, preservative, or a combination of these. 19. The kit of item 18 comprising at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11 or at least least 12 different polypeptides, wherein the amino acid sequence of the T cell epitope of each of the different polypeptides are different from each other.20. The item 18 kit that also includes a prospectus.21. A pharmaceutical composition comprising: a nucleic acid molecule that expresses two or more polypeptides, where each polypeptide is 10-50 amino acids in length and comprises a T cell epitope that binds to at least three HLA class I molecules of the subject and / or at least three HLA class II molecules from the subject, wherein each of the two or more polypeptides comprises a different T cell epitope, wherein the polypeptides do not comprise amino acid sequences that are adjacent to each other in a corresponding antigen. 22. The pharmaceutical composition of item 21, wherein the nucleic acid molecule expresses at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at at least 11 or at least 12 different polypeptides, each of which is 10-50 amino acids in length and comprises an amino acid sequence that is a T cell epitope that binds to at least three HLA class I molecules from the subject and / or or at least three HLA class II molecules from the subject, wherein the amino acid sequence of the T cell epitope of each of the different polypeptides are different from each other. 23. A human subject-specific pharmaceutical composition for the treatment of a disease or disorder in a specific human subject comprising at least one different polypeptide, wherein each of the at least one different polypeptide comprises at least a first and a second region region, where (i) the first region of 10-50 amino acids in length comprises an amino acid sequence that is a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three molecules HLA class II molecule from the subject,(ii) the second region of 10-50 amino acids in length comprises an amino acid sequence that is a T cell epitope that binds to at least three HLA class I molecules from the subject and / or or at least two HLA class II molecules from the subject, wherein the amino acid sequence of the T cell epitope from each of the first region and the second region of each of the at least three different polypeptides co understand different sequences. 24. The specific pharmaceutical composition for a human subject of item 23 comprising at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 , at least 11 or at least 12 different polypeptides.25. The specific pharmaceutical composition for a human subject of item 23 comprising 2-40 different polypeptides.26.The specific pharmaceutical composition for a human subject of item 23, wherein the T-lymphocyte epitope that binds to at least three HLA class I molecules of the subject comprises between 7 and 11 amino acids, and / or the T-lymphocyte epitope that binds to at least three HLA class II molecules comprises between 13 and 17 amino acids.27. The specific pharmaceutical composition for a human subject of item 23, where the epitopes of the first region and the second region are from a single antigen.28. The specific pharmaceutical composition for a human subject of item 23, where the epitopes of the first region and the second region are from two or more different antigens.29. The specific pharmaceutical composition for a human subject of item 27, where the antigen is an antigen expressed by a cancer cell, a neoantigen expressed by a cancer cell, a cancer-associated antigen, a tumor-associated antigen, or an antigen expressed by a target pathogenic organism, an antigen expressed by a virus, an antigen expressed by a bacterium, an antigen expressed by a fungus, an antigen associated with an autoimmune disorder, or is an allergen. 30. The specific pharmaceutical composition for a human subject of item 29, where the cancer cell is from the subject.31. The specific pharmaceutical composition for a human subject of item 27, wherein the antigen is selected from the antigens listed in tables 2 to 7.32. The specific pharmaceutical composition for a human subject of item 23, where the polypeptides have been analyzed to eliminate substantially all neoepitopes that span a junction between the two regions and that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells from the subject; (ii) is a T cell epitope capable of binding to at least two HLA class I molecules from the subject; or(iii) meets the requirements (i) and (ii). 33. The pharmaceutical composition specific for a human subject of item 23, wherein the at least one polypeptide does not comprise any amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T cell epitope capable of binding to at least two HLA class I molecules of the subject. 34. The specific pharmaceutical composition for a human subject of item 23 that also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.35. The specific pharmaceutical composition for a human subject of item 34, wherein 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.36. A method of preparing a human subject-specific pharmaceutical composition for use in a method of treating a specific human subject, wherein the method comprises: (i) selecting a fragment of a polypeptide, wherein this fragment has been identified as immunogenic for the subject a) by determining whether the fragment comprises: 1) an amino acid sequence that is a T cell epitope capable of binding to at least three HLA class I molecules from the subject; or 2) an amino acid sequence that is a T cell epitope capable of binding to at least three HLA class II molecules from the subject; or 3) or meets the requirements (1) and (2); and b) by identifying the sequence as a fragment of the polypeptide that is immunogenic to the subject; (ii) selecting a first sequence of up to 50 consecutive amino acids of the polypeptide, where the consecutive amino acids comprise the amino acid sequence of the fragment selected in step (i); and (iii) preparing a pharmaceutical composition specific for a subject having as active ingredients one or more polypeptides that together have all the amino acid sequences selected in the previous steps. 37.The method of item 36 further comprising, before the preparation step, repeating steps (i) to (ii) to select a second amino acid sequence of up to 50 consecutive amino acids of the same polypeptide or a polypeptide different from the first sequence of amino acids.38. The method of item 37 further comprising, further repeating, before the preparation step, steps (i) to (ii) one or more times to select one or more additional amino acid sequences out of up to 50 consecutive amino acids of the same polypeptide or of polypeptides different from the first and second amino acid sequences.39. The method of item 36 further comprising, prior to the preparation step, selecting a longer fragment of the polypeptide if the fragment selected in step (i) is an HLA class I binding epitope, which longer fragment comprises the fragment selected in step (i); and it is a T cell epitope capable of binding to at least three HLA class II molecules of the subject.40. The method of item 36, wherein each polypeptide consists of one of the selected amino acid sequences or comprises or consists of two or more of the amino acid sequences arranged end-to-end or overlapping in a single linked polypeptide.41. The method of item 36, wherein neoepitopes formed at the junction between any two of the selected amino acid sequences arranged end-to-end in a single linked polypeptide have been analyzed to eliminate substantially all polypeptides comprising a neoepitope amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; (ii) is an epitope of T lymphocytes capable of binding to at least two HLA class I molecules of the subject; or(iii) meets the requirements (i) and (ii). 42. The method of item 36, wherein the polypeptide(s) were analyzed to remove polypeptides comprising an amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T cell epitope capable of binding to at least two HLA class I molecules of the subject. 43. The method of item 36 further comprising determining the HLA class I genotype and the HLA class II genotype of a biological sample from the subject prior to step (i).44. The method of item 43, where the determination of the HLA class I genotype and the HLA class II genotype is performed through sequence-based typing (SBT) methods.45. The method of item 43, wherein HLA class I genotyping and HLA class II genotyping is performed by sequencing, next-generation sequencing, sequence-specific primer (SSP) methods, or sequence-specific oligonucleotide methods sequences (SSO).46. The method of item 43, where the biological sample is blood, serum, plasma, saliva, buccal swab, urine, expiration, cells or tissues.47. The method of item 43, where the biological sample is saliva or a buccal swab.48. A method of treating a cancer in a specific human subject in need thereof comprising administering to a specific human subject a pharmaceutical composition comprising at least one polypeptide, wherein each of the at least one polypeptide is 10-50 amino acids in length and comprises a first amino acid sequence that is a T-lymphocyte epitope that binds to at least three HLA class I molecules of the subject and / or at least three HLA class II molecules of the subject, wherein the T-lymphocyte epitope of each of the at least one polypeptide is from an antigen that is specific for cancer. 49. The method of item 48, wherein the composition comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least lio at least 12 different polypeptides, wherein the amino acid sequence of the T cell epitope of each of the different polypeptides are different from each other, and are from one or more antigens expressed by a cancer cell of the subject.50. The method of item 48, where the composition comprises 2-40 different polypeptides.51.The method of item 48, wherein the T cell epitope that binds to at least three HLA class I molecules of the subject comprises between 7 and 11 amino acids, and / or the T cell epitope that binds to at least three HLA class II molecules comprise between 13 and 17 amino acids.52. The method of item 48, where the composition comprises at least two different polypeptides and the epitopes of the amino acid sequences of the at least two different polypeptides are from a single antigen.53. The method of item 48, where the composition comprises at least two different polypeptides and the epitopes of the at least two different polypeptides are from two or more different antigens.54. The item 48 method, where the antigen(s) are neoantigens expressed by a cancer cell, a cancer-associated antigen, or a tumor-associated antigen.55. The method of item 48, where the antigen(s) are selected from the antigens listed in Table 2.56. The method of item 48, wherein the at least one different polypeptide further comprises up to 10 amino acids flanking the epitope of T cells that are part of a consecutive sequence flanking the epitope on a corresponding antigen.57. The method of item 48, wherein the at least one different polypeptide further comprises up to 10 amino acids flanking the epitope on T cells that are not part of a consecutive sequence flanking the epitope on a corresponding antigen.58. The method of item 48, where the composition comprises at least two different polypeptides and two of the polypeptides are arranged end-to-end or overlap in a linked polypeptide.59. The method of item 58 comprising two or more different linked polypeptides, wherein the two or more different linked polypeptides comprise different epitopes from each other.60. The method of item 59, wherein the bound polypeptides have been analyzed to remove substantially all neoepitopes that span a junction between the two polypeptides and that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells of the subject;(ii ) is a T cell epitope capable of binding to at least two HLA class I molecules of the subject; or(iii) meets the requirements (i) and (ii). 61. The method of item 48, wherein the at least one polypeptide does not comprise any amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T cell epitope capable of binding to at least two HLA class I molecules of the subject. 62. The method of item 48, where the composition also comprises a pharmaceutically acceptable adjuvant, diluent, carrier, preservative or a combination of these.63. The method of item 62, 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.64. The method of item 48 that also includes administering a chemotherapeutic agent, a targeted therapy, radiation therapy, a checkpoint inhibitor, another immunotherapy or a combination of these.65. A human subject-specific pharmaceutical composition for the treatment of a disease or disorder in a specific human subject comprising (a) a polypeptide 10-50 amino acids in length and comprising a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three HLA class II molecules from the subject; and (b) a pharmaceutically acceptable adjuvant.66.The specific pharmaceutical composition for a human subject of item 65 comprising at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at at least 11 or at least 12 different polypeptides, where each of the different polypeptides is 10-50 amino acids in length and comprises a T cell epitope that binds to at least three HLA class I molecules from the subject and / or to the least three HLA class II molecules from the subject, wherein the amino acid sequence of the T cell epitope of each of the different polypeptides are different from each other. 67. The specific pharmaceutical composition for a human subject of item 66 comprising 2-40 different polypeptides.68. The specific pharmaceutical composition for a human subject of item 65, wherein the T-lymphocyte epitope that binds to at least three HLA class I molecules of the subject comprises between 7 and 11 amino acids, and / or the T-lymphocyte epitope that binds to at least three HLA class II molecules comprises between 13 and 17 amino acids.69. The specific pharmaceutical composition for a human subject of item 66 that comprises at least two different polypeptides, where the epitopes of the at least two different polypeptides are from a single antigen.70. The specific pharmaceutical composition for a human subject of item 66 that comprises at least two different polypeptides, where the epitopes of the at least two different polypeptides are from two or more different antigens.71. The specific pharmaceutical composition for a human subject of item 69, where the antigen is an antigen expressed by a cancer cell, a neoantigen expressed by a cancer cell, a cancer-associated antigen, a tumor-associated antigen, or an antigen expressed by a target pathogenic organism, an antigen expressed by a virus, an antigen expressed by a bacterium, an antigen expressed by a fungus, an antigen associated with an autoimmune disorder, or is an allergen.72. The specific pharmaceutical composition for a human subject of item 71, where the cancer cell is from the subject.73. The specific pharmaceutical composition for a human subject of item 69, wherein the antigen is selected from the antigens listed in tables 2 to 7.74. The specific pharmaceutical composition for a human subject of item 69 comprising at least two different polypeptides, wherein two of the polypeptides are arranged end-to-end or overlap in a linked polypeptide.75. The specific pharmaceutical composition for a human subject of item 65, wherein the adjuvant is selected from the group consisting of Montanidc 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. 76. The pharmaceutical composition specific for a human subject of item 65 comprising at least two different polypeptides, wherein two of the at least two polypeptides are arranged end-to-end or overlap in a linked polypeptide.77. The specific pharmaceutical composition for a human subject of item 76 comprising two or more different bound polypeptides, wherein the two or more different bound polypeptides comprise different epitopes from each other.78. The specific pharmaceutical composition for a human subject of item 77, wherein the bound polypeptides have been analyzed to eliminate substantially all neoepitopes that encompass a junction between the two polypeptides and that (i) corresponds to a fragment of a human polypeptide expressed in cells healthy from the subject; (ii) is a T cell epitope capable of binding to at least two HLA class I molecules from the subject; or(iii) meets the requirements (i) and (ii). 79.The specific pharmaceutical composition for a human subject of item 66, wherein the at least two polypeptides do not comprise any amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T cell epitope capable of binding to at least two HLA class I molecules of the subject. 80. A kit comprising: (a) a first pharmaceutical composition specific for a human subject comprising (i) a first polypeptide 10-50 amino acids in length and comprising a T cell epitope that binds to at least three molecules of HLA class I from the subject and / or at least three molecules of HLA class II from the subject; and (ii) a pharmaceutically acceptable adjuvant; (b) a second pharmaceutical composition specific for a human subject comprising (i) a second polypeptide 10-50 amino acids in length and comprising a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three HLA class II molecules from the subject; and (ii) a pharmaceutically acceptable adjuvant, wherein the first polypeptide and the second polypeptide comprise different T cell epitopes. 81. The kit of item 77, wherein the first composition and / or the second composition comprise one or more additional polypeptides , wherein each additional polypeptide is 10-50 amino acids in length and comprises an amino acid sequence that is a T cell epitope that binds to at least three HLA class I molecules from the subject and / or at least three HLA class I molecules from the subject. HLA class II of the subject, wherein the amino acid sequences comprise different epitopes of T cells. 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 was determined with the experimentally determined data set (Table 9). 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 9. Analytical specificity and sensitivity of the HLA-epitope binding prediction process. 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 10. 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 conducted by retrospective analysis of six clinical trials, conducted in 71 cancer patients and 9 HIV-infected patients (Table 11)1"7. Patients in these studies were treated with one HPV vaccine, three cancer-specific vaccines of different NY-ESO-1, an HIV-1 vaccine, and a CTLA-4-specific monoclonal antibody (Ipilimumab) that was shown to reactivate CTLs against the NY-ESO-1 antigen in melanoma patients.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 11) were randomized with a standard random number generator to create two independent cohorts for the studies. training and evaluation. 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. Table 11. Compendium of patient data sets 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. They were obtained antigen sequences and HLA I genotype of each patient 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 patients. 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 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 12). Table 12. Determination of the diagnostic value of the PEPT biomarker by ROC analysis. An individual's CTL response was best predicted by considering the epitopes of an antigen that could be presented by at least 3 HLA class I from an individual (PEPI3+, AUC=0.65, Table 12). The PEPI3+ threshold 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 13). 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 13). Table 13. Determination of <1 PEPI3+ threshold for predicting likely CTL responders in the training data set. 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 14). 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 10). These data provide strong evidence that immune responses are induced by PEPI in individuals. Table 14. 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 15). This result confirmed the threshold determined during training (Table 12). Table 15. 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 that cover 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 HLA 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 HLA Class II Restricted CD4+ T Helper 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 (FIG. 4). 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 PEPI3+ 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 5). 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 5-6 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 ( ΡΕΡΙ3+), 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 HPV-16 antigens and the two HPV antigens -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 seen 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 perform 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 correlated significantly with the large population (Table 16) (Pearson p<.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 16. 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 vaccine peptides have been determined from of 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). Table 17. Clinical trials conducted with peptide vaccines. 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 18). We also found a linear correlation 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 in an individual is useful for in silico predicting the outcome of clinical trials. Table 18. Comparison of PEPI3+ <1 scores and CTL response rates of 12 peptide vaccines. * % of subjects in model population with =1 / PEPI3+ derived from vaccine 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 by testing for <1 PEPI3+ 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. * % of subjects in the model population with vaccine-derived fl PEPI3+ 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 to enhance the T cell responses against kidney cancer in trial subjects, because their presence has been detected in kidney cancer patients, and because trial patients were specifically selected to have at least one HLA molecule capable of presenting each one 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 21). Table 21. 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 test of <2 PEP13+ 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 responses immune 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 immunotherapy vaccines determined in the model population described in Example 8 and the reported disease control rate (DCR, proportion of patients with complete responses 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 (Tables 22). 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 23 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 22. Selected clinical trials for disease control rate (DCR) prediction. related with HPV *Montanide ISA51 VG as adjuvant **Disease response was assessed according to the International Myeloma Task Force response criteria45 Table 23. Disease Control Rates (DCR) and MultiPEPI Scores (Predicted DCR) in 17 Clinical Trials. Example 13 - The Set of Multiple HLA-Binding Peptides of Tumor Antigens Predicts Responders to Ipilmumab Checkpoint Inhibitor Immunotherapy We determined whether the survival benefit of melanoma patients treated with the checkpoint inhibitor ipilimumab could be predicted by the amount of melanoma-specific PEPI3+ that are potentially expressed in the patient's tumor. Eighty melanoma-associated antigens (TAA) were identified from which a panel of PEPI3+ was selected (IPI-PEPI panel: 627 PEPI) that are shared by ipilimumab-treated melanoma patients with prolonged clinical benefit and are absent in those without. have prolonged clinical benefit. These PEPI3+ define the specific T lymphocytes that are reactivated by Ipilimumab to attack the patient's tumor cells. Patients with certain HLA sequences who may have more melanoma-specific PEPIs have more ipilimumab-reactivated T cells and are more likely to benefit from ipilimumab therapy. Ipilimumab immunotherapy. The clinical benefit of ipilimumab treatment was determined for 160 patients from four independent clinical trial cohorts. The cohorts were from trials CA184-007 (Ipilimumab 10 mg / kg) and CAI84-002 (Ipilimumab 3 mg / kg) and two cohorts from published clinical trial databases with 10 mg / kg and 3 / mg / kg. kg of Ipilimumab5,38'39. Epitopes of 80 melanoma antigens restricted to all 6 HLA class I from each patient were predicted and then the number of melanoma-specific PEPI3+ restricted to at least 3 HLA class I from each patient (4,668 PEPI) was calculated. Every patient with at least one of 627 PEPI qualified as a responder. The IPI-PEPI panel predicts overall survival for Ipilimumab 10 mg / kg and 3 mg / kg. The results were highly significant and consistent with the four independent cohorts (figure 10). Example 14: Multiple HLA Binding Epitopes Define Patient Mutational Neoantigens The ability of PEPI3+ to identify mutational neoantigens was determined. PEPI3+ of 110 melanoma patients treated with ipilimumab were determined using published exorn mutation data39. From the exorn mutation data, mutations occurred in 9,502 antigens from 110 patients (FIG. 11A). The mean non-synonymous mutational burden per sample was highly variable, 309 (29-4,738) in the clinical benefit cohort and 147 (7-5,854) in the minimal or no clinical benefit cohort. Due to their epitope prediction results, these mutations had 211 (8-1950) and 56 (2-3444) neoepitopes in the clinical benefit cohort and the minimal clinical benefit and no clinical benefit cohorts, respectively. Mutational PEPI3+ neoepitopes of the published mutations were determined (FIG. 11B and Table 24). These mutations produced median 16 PEPI and 6 PEPI neoepitopes in the clinical benefit cohort and the minimal clinical benefit or no clinical benefit cohorts, respectively. The results show that PEPIs define mutational neoantigens derived from genetically altered proteins expressed in an individual. Said neoantigens are PEPI3+ peptides capable of activating T lymphocytes in the patient's body. If a genetic alteration occurs in the individual's tumor cell that creates a PEPI3+, this PEPI3+ can induce T cell responses. These PEPI3+ containing peptides can be included in a drug (eg, vaccine, T cell therapy) to induce an immune response against the individual's tumor. Table 24. Prediction of neoantigen mutations using the PEPI test: analysis results of the Van Alien et al. and the PEPI test in 110 patients with melanoma. Example 15 In silico assays based on the identification of multiple HLA-binding epitopes predicting rates of cellular immune response indicated for a mutational antigen-directed vaccine Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation that is widely expressed in glioblastoma multiforme (GBM) and other neoplasms. The mutation involves an 801 bp in-frame deletion of the EGFR extracellular domain that splits a codon and produces a novel glycine at the fusion junction.1, 2 This mutation encodes a constitutively active tyrosine kinase that increases formation of the tumor and tumor cell migration and improves resistance against radiation and chemotherapy.3, 4' 5' 6' 7' 8' 9 This insert produces a tumor-specific epitope that is not found in normal adult tissues, making EGFRvIII a suitable target candidate for antitumor immunotherapy.10 Rindopepimut is a 13-amino acid peptide vaccine (LEEKKGNYVVTDHC) that encompasses the EGFRvIII mutation with an additional C-terminal cysteine ​​residue.11 In a phase II clinical study, keyhole limpet hemocyanin-conjugated peptide (KLH) was administered to patients with newly diagnosed EGFRvIII-expressing GBM. The first three vaccinations were given biweekly, beginning 4 weeks after radiation completion. Subsequent vaccinations were given monthly until radiographic evidence of tumor progression or death was obtained. All vaccines were administered intradermally in the inguinal region. Immunological evaluation showed only 3 of 18 patients who developed cellular immune response evaluated by DTH reaction test. An in silico test was performed with the model population of 433 subjects with the Rindopepimut sequence. 4 of 433 subjects had PEPI3+, confirming the low immunogenicity found in the phase II study (Table 25). Table 25. Results of the clinical trial and the in silico study. An HLA map of Rindopepimut on the HLA alleles of subjects in the model population (Figure 12) illustrates that very few HLA-A and HLA-C alleles can bind the vaccine epitopes, which explains the lack of PEPI3+ in the in silico cohort. In a recent phase 1 clinical study11, inefficacy was demonstrated when 745 patients participated and were randomly assigned to Rindopepimut and temozolomide (n=371) or control and temozolomide (n=374) groups.12 The trial was canceled due to inefficacy after interim analysis. The analysis showed no significant difference in overall survival: median overall survival was 20.1 months (95% CI 18.5-22.1) in the Rindopepimut group versus 20.0 months (18.1-21 .9) in the control group (HR 1.01, 95% Cl 0.79-1.30; p=0.93). References for Example 15 1 Bigner et al. Characterization of the epidermal growth factor receptor in human glioma cell lines and xenografts. Cancer Res 1990;50:8017-22.2 Libermann et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumors of glial origin. Nature 1985;313:144-7.3 Chu et al. Receptor dimerization is not a factor in the signaling activity of a transforming variant epidermal growth factor receptor (EGFRvIII). Biochem J 1997; 324: 855-61.4 Batra et al. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ 1995;6:1251-9.5 Nishikawa et al. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. PNAS 1994; 91: 7727-31.6 Lammering et al. Inhibition of the type III epidermal growth factor receptor variant mutant receptor by dominant-negative EGFR-CD533 enhances malignant glioma cell radiosensitivity. Clin Cancer Res 2004; 10: 6732-43.7 Nagane et al. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res 1996; 56: 5079-86.8 Lammering et al. Radiation-induced activation of a common variant of EGFR confers enhanced radioresistance. Radiother Oncol 2004; 72: 267-73.9 Montgomery et al. Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters β-tubulin isotype expression. J Biol Chem 2000; 275: 17358-63.10 Humphrey et al. Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. PNAS 1990; 87: 4207-11.11 Sampson et al. Immunologic Escape After Prolonged Progression-Free Survival With Epidermal Growth Factor Receptor Variant III Peptide Vaccination in Patients With Newly Diagnosed Glioblastoma. I Clin Oncol 28:4722-4729.12 Wcllcr et al. Rindopcpimut with tcmozolomidc for patients with newly diagnosed, EGFRvIII- expressing glioblastoma (ACT IV): a randomized, double-blind, international phase 3 trial. Lancet Oncol 2017; 18(10): 1373-1385. Example 16. Multiple HLA-binding Peptides from Individuals Can Predict Immunotoxicity Thrombopoietin (TPO) is a highly immunogenic protein drug that causes toxicity in many patients. EpiVax / Genentech used state-of-the-art technology to identify HLA class II restricted epitopes and found that the most immunogenic region of TPO is located at the C-terminus of TPO (US20040209324 Al). In accordance with the present disclosure, multiple HLA class II binding epitopes (PEPI3+) of TPO were determined in 400 genotyped HLA class II US subjects. Most of the PEPI3+ peptides from these individuals are located within the N-terminal region of TPO between amino acids 1-165. PEPI3+ were sporadically identified in some subjects also in the C-terminal region. However, these results were different. of those of the state of the art. The published literature confirmed the results described, demonstrating experimental proof that the immunotoxic region is located at the N-terminus of TPO40,41. Most individuals treated with the TPO drug produced ADA anti-drug antibodies (ADAs) against this region of the drug. These antibodies not only eliminated the therapeutic effect of the drug, but also caused systemic adverse events, that is, immunotoxicity, such as antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity associated with thrombocytopenia, neutropenia, and anemia. These data demonstrate that the identification of multiple HLA-binding peptides from individuals predicts the immunotoxicity of TPO. Thus, the description is useful for identifying the toxic immunogenic region of drugs, for identifying subjects likely to experience drug immunotoxicity, for identifying regions of a polypeptide drug that can be targeted by ADAs, and for identifying subjects likely to have ADA. Example 17 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 specifically designed for the patient based on her HLA genotype according to the description described herein. This example and Example 19 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 26). In addition, each peptide is optimized to bind to the maximum amount of HLA class II in the patient. Table 26: 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 10. 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 should be 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 Figure 13. 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 26), since it was determined that the presence in an immunotherapy or vaccine composition of at least two polypeptide fragments (epitopes) that can bind to at least three HLAs 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 series / month), treatment with ΡΓΓ vaccine started on April 21, 2017. Table 27 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. The use of MRI limits the detection of lung (pulmonary) metastases • May 2016 - January 2017: Olaparib treatment • 25 / Dec / 2016 (before treatment with ΡΓΓ vaccine) There was a dramatic reduction in tumor burden with confirmation of 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 leading to disease progression• April 21, 2017 INITIAL PIT• July 21 / 17 (after the 2nd cycle of PIT) FU4 demonstrated continued growth of lesions, general enlargement of the pancreas, and abnormal parapancreatic signal along with increased ascites• 26 / Jul / 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 28 and Figure 14. Table 28. Injury Response Compendium Table Example 18 Design of personalized immunotherapy composition for the treatment of breast cancer The HLA class I and class II genotype of the patient with breast cancer was determined metastatic ABC 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 class I HLAs from patient ABC (Table 29). 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 15. Table 29. 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 ΡΓΓ vaccine. He was feeling very well and refused PET CT in September 2017. In November he developed symptoms, PET scan showed progressive disease, but refused all treatment. Also, the oncologist discovered that he had not taken Palbocyclib since the spring / summer. Patient ABC passed away in January 2018. The combination of pablocyclib and the personalized vaccine is likely to have been responsible for the remarkable rapid response observed after administration of the vaccine. Palbocyclib has been shown to enhance the activity of immunotherapies by increasing the presentation of CTA by HLAs and decreasing the proliferation of Trcgs: (Gocl et al. Naturc. 2017:471-475). The PIT vaccine can be used as an adjunct to next-generation therapy for maximum efficacy. Example 19 - 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 before treatment with the PIT vaccine) 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 30). Peptides PBRC05-P01-P10 were prepared for this patient based on population expression data. The last 3 peptides in Table 29 (SSX-2, MORC, MAGE-B1) were designed from antigens whose expression was measured directly in the patient's tumor. Table 30 - Vaccine peptides for patient BRC05 Note: bold and red means CD8 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, PBRC05_P6, PBRC05_P7. Table 31 - 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. Example 20 - Personalized immunotherapy composition for the treatment of a patient with metastatic breast cancer in an early stage BACKGROUND: In 2011, she left the excision of the breast sector due to a neoplasm. Treatment: aromatase inhibitor and irradiation of the lumbar spine (bone metastases). In 2017, before administering the PIT vaccine treatment, a metastatic lesion was observed in the ventral arch of the right 5th rib and in the right 3rd rib. In the left breast, the possibility of a recurrent malignant neoplasm must be ruled out. In the right breast there may be a malignancy with metastatic right axillary lymph node. Table 32 - Vaccine peptides for the patient of example 20 The patient obtained 2 cycles of PIT vaccine. Example 21 - Characterization of toxicity - immunoBLAST A method was developed to perform 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. can be generated neoepitopes in the junction region of the two 15-mer peptides and can induce unwanted T cell responses against healthy cells (autoimmunity). This was 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 Fig. 16, 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 PEPT3+ test was used to identify neoepitopes and neoPEPT 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 33. 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 PolyPEPI1018 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 33 - Identification of possible neoepitopes of PolyPEPI1018 Abbreviations: CRC = colorectal cancer; HLA = human leukocyte antigen; PEPI = personal epitope REFERENCES 1 Bagarazzi et al. Immunotherapy against HPV16 / 18 general 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 J Med. 2009; 361(19):1838-47.10 Wcltcrs et al. Succcss or failurc of vaccination for HPV16-positivc vulvar lcsions 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 Mar 7, 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 MUCl-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 WTl-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 Stage IV 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(l):92-9. 25Fcnoglio et al. A multi-pcptidc, dual-adjuvant tclomcrasc vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer. Cancer Immunol Immunother; 2013; 62:1041-1052. 26Krug 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. 27Slingluff 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. 28Hodi et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med; 2010;363(8):711-23. 29 Carmon et al. Phase VII 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 Mar 28, 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. 32Cusi et al. Phase I trial of thymidylate synthase poly epitope peptide (TSPP) vaccine in advanced cancer patients. Cancer Immunol Immunother; 2015; 64:1159-1173. 33Asahara et al. Phase T / TT clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic cancer. J Transit Med; 2013;l 1:291. 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. 36Rapoport et al. Combination Immunotherapy after ASCT for Multiple Myeloma Using MAGE-A3 / Poly-ICLC Immunizations Followed by Adoptive Transfer of Vaccine-Primed and Costimulatcd Autologous T Cells. Clin Cancer Res; 2014; 20(5): 1355-1365. 37Greenfield et al. A phase I 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, 031439. 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 Takedatsu et al. Determination of Thrombopoietin-Derived Peptides Recognized 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). EurJ 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 method for predicting whether a polypeptide or a fragment of a polypeptide is immunogenic for a specific human subject, wherein the method comprises the steps of (i) determining whether the polypeptide comprises: (a) an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class I molecules of the subject; or (b) an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class II molecules of the subject; and (ii) predicting A. that the polypeptide is immunogenic for the subject if the polypeptide comprises at least one sequence that meets the requirements of step (i); or B. that the polypeptide is not immunogenic for the subject if the polypeptide does not comprise at least one sequence that meets the requirements of step (i).

2. A method for identifying a polypeptide fragment as immunogenic to a specific human subject, wherein the method comprises the steps of (i) determining that the polypeptide comprises: (a) an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class I molecules of the subject; or (b) an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class P molecules of the subject; and (ii) identifying such sequence as a polypeptide fragment that is immunogenic to the subject.

3. The method of claim 1 or claim 2, wherein the T-cell epitope is capable of binding to at least two subject class I HLA molecules and consists of 9 consecutive amino acids of the polypeptide, or wherein the T-cell epitope is capable of binding to at least two subject class II HLA molecules and consists of 15 consecutive amino acids of the polypeptide.

4. The method of any of the preceding claims, wherein step (i) comprises determining that the polypeptide comprises an amino acid sequence that is a T-cell epitope capable of binding to at least two subject class I HLA molecules.

5. The method of any of the preceding claims, wherein step (i) comprises determining that the polypeptide comprises an amino acid sequence that is a T-cell epitope capable of binding to at least three subject class I HLA molecules.

6. The method of any of claims 1 to 3, wherein step (i) comprises determining that the polypeptide comprises an amino acid sequence that is a T-cell epitope capable of binding to at least three subject class II HLA molecules.

7. The method of claim 4 or claim 5 further comprising identifying a fragment of the polypeptide that is a T-cell epitope capable of binding to at least one subject class II HLA molecule, wherein the class II HLA-binding epitope comprises the amino acid sequence of the class I HLA-binding T-cell epitope. 8.The method of any of the preceding claims, wherein the polypeptide is expressed by a pathogenic organism, a virus, or a cancer cell, is associated with an autoimmune disorder, or is an allergen or an ingredient of a pharmaceutical composition.

9. The method of any of the preceding claims, wherein the polypeptide is selected from the antigens listed in Tables 2 to 6.

10. The method of any of the preceding claims, wherein the polypeptide is an antigen or neoantigen expressed by a cancer cell, wherein, optionally, the cancer cell, the antigen, or the neoantigen is found in a sample taken from the subject.

11. The method of any of the preceding claims, wherein the polypeptide is a mutational neoantigen, wherein, optionally, (a) the neoantigen is present in a sample obtained from the subject; and / or (b) the immunogenic fragment comprises a specific neoantigen mutation.

12. The method of any one of claims 1 to 11, wherein all polypeptide fragments that are a T lymphocyte epitope capable of binding to at least two HLA class I molecules and / or all polypeptide fragments that are a T lymphocyte epitope capable of binding to at least two HLA class II molecules of the subject are identified, wherein, optionally, the method is repeated for each polypeptide that is an active ingredient of a specific pharmaceutical composition.

13. The method of any of the preceding claims further comprising predicting whether the subject will have a cytotoxic T-cell response or a helper T-cell response to the administration of one or more polypeptides or a pharmaceutical composition or kit comprising one or more polypeptides as active ingredients, wherein A. predicts a cytotoxic T-cell response if the polypeptides comprise at least one amino acid sequence that is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject; B. predicts a helper T-cell response if the polypeptides comprise at least one amino acid sequence that is a T-cell epitope capable of binding to at least three HLA class II molecules of the subject; C.No cytotoxic T cell response is predicted if the polypeptides do not comprise any amino acid sequence that is a T cell epitope capable of binding to at least three subject class I HLA molecules; or D. No helper T cell response is predicted if the polypeptides do not comprise any amino acid sequence that is a T cell epitope capable of binding to at least three subject class II HLA molecules.

14. The method of claim 13, wherein it is predicted that the subject will have a cytotoxic T lymphocyte response and / or a helper T lymphocyte response, and the method further comprises determining the probability that the subject will have a cytotoxic T lymphocyte response and / or a helper T lymphocyte response directed against a polypeptide antigen expressed on the subject, wherein the method comprises (i) identifying one or more polypeptide antigens comprising an amino acid sequence that (a) is a T lymphocyte epitope capable of binding to at least three HLA class I molecules or at least three HLA class II molecules of the subject;and (b) is included in the amino acid sequence of the polypeptides (ii) using population expression frequency data for the polypeptide antigen(s) identified in step (i) to determine the likelihood that the subject will have a cytotoxic T lymphocyte response and / or a helper T lymphocyte response directed to a polypeptide antigen expressed in the subject.; 15. The method of claim 13, wherein the polypeptide is a component of a pharmaceutical composition and the method comprises determining the probability of the subject developing antidrug antibodies (ADA) after administration of the polypeptide, wherein a predicted helper T cell response corresponds to a higher probability of ADA and no predicted helper T cell response corresponds to a lower probability of ADA.

16. The method of claim 15, wherein the polypeptide is a checkpoint inhibitor. 17.The method of any one of claims 1 to 14 further comprising predicting whether the subject will have a clinical response to the administration of a pharmaceutical composition, kit, or polypeptide panel comprising one or more polypeptides as active ingredients, wherein the method comprises determining whether the active ingredient polypeptide(s) together comprise at least two 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 predicting A. that the subject will have a clinical response to the administration of the pharmaceutical composition, kit, or polypeptide panel if the active ingredient polypeptide(s) together comprise at least two different sequences, each of which is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject; or B.that the subject will not have a clinical response to the administration of the pharmaceutical composition, kit or polypeptide panel if the active ingredient's polypeptides together comprise no more than one sequence that is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject.

18. The method of claim 17, 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.19.The method of any of claims 1 to 14, 17 and 18 further comprising determining the probability of a specific human subject having a clinical response to the administration of a pharmaceutical composition, kit or polypeptide panel comprising one or more polypeptides as active ingredients, 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, 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 HLA 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 HLA of the subject.

20. The method of any of claims 1 to 14 and 17 to 19 further comprising determining the probability that the specified human subject will have a clinical response to the administration of a pharmaceutical composition, kit, or polypeptide panel comprising one or more polypeptides as active ingredients, 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.(i) is a T-cell epitope capable of binding to at least three class I HLA of the subject; (ii) use 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) determine the probability that the subject will have a clinical response to the administration of the pharmaceutical composition, kit, or polypeptide panel, wherein a higher probability determined in step (ii) corresponds to a more likely clinical response.

21. The method of claim 20, wherein step (ii) comprises using population expression data for each antigen identified in step (i) to determine the probability that the subject expresses two or more of the antigens identified in step (i) which together comprise at least two different amino acid sequences from step (i).

22. The method of claim 21, 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. 23.The method of any of claims 19 to 22, wherein one or more of the following factors correspond to a greater likelihood 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, each of which is a T-cell epitope capable of binding to at least three class II HLA molecules 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-cell epitope capable of binding to at least three class II HLA molecules of the subject, wherein, optionally, the target polypeptide antigens are expressed in the subject, and wherein, optionally, the target polypeptide antigens are found in one or more samples obtained from the subject; (c) a greater number of target polypeptide antigens comprising i.(d) 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 (e) 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 II HLAs of the subject; (d) a higher probability that the subject will express target polypeptide antigens, optionally a threshold amount of the 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 II HLAs of the subject; (e) a higher probability that the subject will express target polypeptide antigens, optionally a threshold amount of the target polypeptide antigens that have been determined to comprise i.(f) 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 (ii) 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 II HLAs of the subject; (f) a greater number of target polypeptide antigens that the subject is predicted to express, optionally a greater number of target polypeptide antigens that the subject expresses with a threshold probability and 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 II HLAs of the subject; and / or (g) 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 that have been determined to comprise i. 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 ii. 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 II HLAs of the subject.

24. The method of any one of claims 19 to 23 further comprising repeating the method for one or more additional pharmaceutical compositions, kits, or polypeptide panels and ranking the compositions, kits, or polypeptide panels by their likelihood of inducing a clinical response in the subject.

25. The method of any one of claims 1 to 24 further comprising predicting whether administration of the polypeptide, pharmaceutical composition, kit, or polypeptide panel will induce a toxic immune response in the subject, wherein (a) the polypeptides comprise at least one amino acid sequence that i. is capable of binding to at least three class I HLA molecules of the subject; and ii. corresponds to a fragment of a human polypeptide expressed in healthy cells; and a toxic immune response is predicted; or (b) the polypeptides do not comprise any amino acid sequence that A. is capable of binding to at least three class I HLA molecules of the subject; and B.It corresponds to a fragment of a human polypeptide expressed in healthy cells; and no toxic immune response is predicted.

26. The method of any of the preceding claims further comprising selecting or recommending for the treatment of the specific human subject the administration to the subject of a polypeptide comprising a polypeptide fragment identified as immunogenic for the subject, or of a polypeptide predicted to be immunogenic or to induce a cytotoxic T-cell or helper T-cell response, or of a pharmaceutical composition, kit, or panel of polypeptides predicted to induce a clinical response, or of a polypeptide or pharmaceutical composition predicted not to induce a toxic immune response or not to induce ADA in the subject.

27. The method of claim 26 further comprising administering one or more of the selected polypeptides or pharmaceutical compositions or the polypeptides from one or more kits or panels of polypeptides to the subject.

28. A method for treating a human subject in need thereof,wherein the method comprises administering to the subject a polypeptide comprising a polypeptide fragment that has been identified as immunogenic, or a polypeptide that was predicted to be immunogenic, or a polypeptide or pharmaceutical composition that was predicted to induce a cytotoxic T lymphocyte or helper T lymphocyte response, or a pharmaceutical composition, kit or panel of polypeptides that was predicted to induce a clinical response, or a pharmaceutical composition, kit or panel of polypeptides that was determined to have a minimum threshold probability of inducing a clinical response, or a polypeptide or pharmaceutical composition that was predicted not to induce a toxic immune response or development of ADA in the subject using a method according to any one of claims 1 to 23,or one or more polypeptides or pharmaceutical compositions that have been selected or recommended for the treatment of the subject using a method according to claim 26., 29. The method of any of claims 1 to 11, wherein the polypeptide is associated or suspected to be associated with an autoimmune disorder or autoimmune response in the subject, determining that the polypeptide comprises an amino acid sequence that is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject, identifying the polypeptide and / or fragment as immunogenic or associated with the autoimmune disorder or autoimmune response in the subject. 30.The method of any one of claims 1 to 12 further comprising predicting whether the subject will have a clinical response to the administration of a checkpoint inhibitor for treating cancer, wherein the method comprises determining whether one or more cancer-associated antigens together comprise at least two different amino acid sequences, each of which is a T-cell epitope capable of binding to at least three class I HLA molecules of the subject and predicting A. that the subject will have a clinical response to the administration of a checkpoint inhibitor if the cancer-associated antigen(s) together comprise at least two different sequences, each of which is a T-cell epitope capable of binding to at least three class I HLA molecules of the subject; or B.that the subject will not have a clinical response to the administration of a checkpoint inhibitor if the cancer-associated antigen(s) together comprise no more than one sequence that is a T-cell epitope capable of binding to at least three HLA class I molecules of the subject.

31. The method of any one of claims 1 to 12 further comprising determining the likelihood of the subject having a clinical response to the administration of a checkpoint inhibitor for treating cancer, wherein the method comprises (i) selecting multiple polypeptide antigens that are associated with the subject's cancer type; (ii) identifying which of said cancer-associated antigens comprise an amino acid sequence that is a T-cell epitope capable of binding to at least three of the subject's class I HLA molecules;and (iii) using population expression data for each cancer-associated antigen identified in the stage to determine the likelihood of the subject having a clinical response to the administration of a checkpoint inhibitor to treat cancer, wherein a higher likelihood of the subject expressing one or more of the cancer-associated antigens identified in stage (ii) that together comprise at least two amino acid sequences, each of which is a T-cell epitope capable of binding to at least three of the subject's class I HLA molecules, corresponds to a more likely clinical response.

32. The method of claim 30 or claim 31 further comprising selecting or recommending the administration of a checkpoint inhibitor for the treatment of the subject.

33. The method of claim 32 further comprising administering a checkpoint inhibitor to the subject.

34. A method of treating a human subject in need thereof, wherein the method comprises administering a checkpoint inhibitor to the subject, wherein the subject is predicted to respond, or is likely to respond, to the administration of a checkpoint inhibitor by a method according to claim 30 or claim 31.

35. The method of any one of claims 13, 15 to 18, and 30, wherein the subject is predicted to have a toxic immune response or develop ADA, or not have a cytotoxic T-cell, helper T-cell, or clinical response.or does not respond to treatment with a checkpoint inhibitor, and the method further comprises selecting or recommending a different treatment for the subject.

36. A method for designing or preparing a pharmaceutical composition specific to a human subject or a kit or panel of polypeptides for use in a method of treating a specific human subject, wherein the method comprises: (i) selecting a fragment of a polypeptide, wherein this fragment has been identified as immunogenic for the subject by the method according to any one of claims 2 to 11; (ii) if the fragment selected in step (i) is an HLA class I binding epitope, optionally selecting a longer fragment of the polypeptide,wherein said longer fragment a. comprises the fragment selected in step (i); and b. is a T-cell epitope capable of binding to at least three or as many as possible of the subject's class II HLA molecules; (iii) selecting a first sequence of up to 50 consecutive amino acids from the polypeptide,wherein the consecutive amino acids comprise the amino acid sequence of the fragment selected in step (i) or the longest fragment selected in step (ii); (iv) repeating steps (i) to (iii) to select a second amino acid sequence of up to 50 consecutive amino acids from the same polypeptide or a different polypeptide from the first amino acid sequence; (v) optionally further repeating steps (i) to (iii) to select one or more additional amino acid sequences of up to 50 consecutive amino acids from the same polypeptides or different polypeptides from the first and second amino acid sequences; and (vi) designing or preparing a subject-specific pharmaceutical composition, kit, or polypeptide panel having as active ingredients one or more polypeptides that together have all the amino acid sequences selected in the preceding steps,optionally where one or more or each sequence is flanked at the N and / or C end by additional amino acids that are not part of the polypeptide sequence.

37. The method of claim 36, wherein each polypeptide consists of one of the selected amino acid sequences or comprises two or more of the amino acid sequences arranged end-to-end or overlapping in a single peptide.

38. The method of claim 37, wherein all neoepitopes formed at the junction between any two of the selected amino acid sequences arranged end-to-end in a single polypeptide have been analyzed to eliminate polypeptides comprising a neoepitope amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; (ii) is a T-cell epitope capable of binding to at least two subject class I HLA molecules; or (iii) meets requirements (i) and (ii).

39. The method of any of claims 36 to 38, wherein the polypeptide(s) were analyzed to remove polypeptides comprising an amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T-cell epitope capable of binding to at least two subject class I HLA molecules.

40. A pharmaceutical composition specific to a human subject, a kit or a panel of polypeptides for use in a method for inducing an immune response in a specific human subject, and designed or prepared for the subject according to the method of any of claims 36 to 39, wherein the composition or kit optionally comprises at least one pharmaceutically acceptable diluent, carrier or preservative.41.A pharmaceutical composition, kit, or panel of polypeptides for use in a treatment method for a specific human subject in need thereof, wherein the composition, kit, or panel comprises as active ingredients a first and a second peptide and optionally one or more additional peptides, wherein each peptide comprises an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class I molecules and / or at least two HLA class II molecules of the subject, wherein the amino acid sequence of the T-cell epitope of the first, second, and optionally any additional peptides are different from each other, and wherein the pharmaceutical composition or kit optionally comprises at least one pharmaceutically acceptable diluent, carrier, or preservative.

42. A human subject-specific pharmaceutical composition, kit, or polypeptide panel for use in a treatment method for a specific human subject in need thereof, wherein the composition or kit comprises as an active ingredient a polypeptide comprising a first region and a second region and optionally one or more additional regions, wherein each region comprises an amino acid sequence that is a T-cell epitope capable of binding to at least two HLA class I molecules and / or at least two HLA class II molecules of the subject, wherein the amino acid sequence of the T-cell epitope of the first, second, and optionally any additional regions are different from each other, and wherein the pharmaceutical composition or kit optionally comprises at least one pharmaceutically acceptable diluent, carrier, or preservative. 43.The human subject-specific pharmaceutical composition, kit, or panel of claim 41 or claim 42, wherein one or more or each of the peptides or regions comprise an amino acid sequence that is a T-cell epitope capable of binding to at least two subject class I HLA molecules.

44. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 43, wherein one or more or each of the peptides or regions comprise an amino acid sequence that is a T-cell epitope capable of binding to at least three subject class I HLA molecules.

45. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 44, wherein one or more or each of the peptides or regions comprise an amino acid sequence that is a T-cell epitope capable of binding to at least three subject class II HLA molecules. 46.The human subject-specific pharmaceutical composition, kit, or panel of claim 44 or claim 45, wherein one or more or each of the peptides or regions comprise an amino acid sequence that is a T-cell epitope capable of binding to at least one subject class II HLA molecule, wherein the class II HLA-binding T-cell epitope comprises an amino acid sequence that is a T-cell epitope capable of binding to at least two subject class I HLA molecules.

47. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 46, wherein one or more or each of the peptides or regions comprises a sequence of up to 50 consecutive amino acids from a polypeptide that is expressed by a pathogenic organism, a virus, or a cancer cell, is associated with an autoimmune disorder, or is an allergen, wherein the sequence comprises the T-cell epitope of the peptide or region that is capable of binding to at least two HLA class I or class II molecules of the subject, wherein, optionally, one or more or each of the polypeptide sequences is flanked at the N and / or C terminus by additional amino acids that are not part of the amino acid sequence of the polypeptides. 48.The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 47, wherein one or more of the polypeptides are selected from the antigens listed in Tables 2 to 6.

49. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 48, wherein the polypeptides are antigens or neoantigens expressed by a cancer cell, wherein, optionally, the cancer cell is found in a sample taken from the subject.

50. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 49, wherein the polypeptides are mutational neoantigens, wherein, optionally, the neoantigens are present in a sample obtained from the subject; and / or each of the T-cell epitopes comprises a specific neoantigen mutation. 51.The human subject-specific pharmaceutical composition, kit, or panel of any of claims 47 to 50, wherein two or more or each of the polypeptide sequences of up to 50 consecutive amino acids are from different polypeptides.

52. The human subject-specific pharmaceutical composition, kit, or panel of any of (a) comprises an amino acid sequence that is a T-cell epitope capable of binding to at least three subject class I HLA molecules; and (b) is a T-cell epitope capable of binding to at least three subject class II HLA molecules or to the greatest possible number of subject class II HLA molecules for a sequence comprising the class I HLA-binding epitope of (a).

53. The human subject-specific pharmaceutical composition, kit, or panel of claims 47 to 52 wherein one or more or each polypeptide (a) consists of one of said sequences of up to 50 consecutive amino acids from a polypeptide that is expressed by a pathogenic organism, a virus, or a cancer cell, is associated with an autoimmune disorder, or is an allergen; or (b) comprises or consists of two or more of said sequences of up to 50 consecutive amino acids arranged end-to-end or overlapping in a single peptide.

54. The human subject-specific pharmaceutical composition, kit, or panel of claim 53, wherein the peptide(s) do not comprise any neoepitope encompassing a linkage between any two of said amino acid sequences arranged end-to-end in a single peptide and which (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; (ii) is a T-cell epitope capable of binding to at least two subject class I HLA molecules; or (iii) meets requirements (i) and (ii).

55. The human subject-specific pharmaceutical composition, kit, or panel of any of claims 41 to 54, wherein the polypeptide(s) do not comprise any amino acid sequence that (i) corresponds to a fragment of a human polypeptide expressed in healthy cells; or (ii) corresponds to a fragment of a human polypeptide expressed in healthy cells and is a T-cell epitope capable of binding to at least two subject class I HLA molecules.

56. A treatment method comprising administering to a human subject in need a human subject-specific pharmaceutical composition or the polypeptides from a polypeptide kit or panel according to any one of claims 41 to 55, wherein the pharmaceutical composition, kit, or panel is subject-specific, and wherein, optionally, the method is for the treatment of cancer.

57. The treatment method according to any one of claims 28, 34, and 56, wherein the treatment is administered in combination with chemotherapy, targeted therapy, or checkpoint inhibitors. 58.A method for designing or preparing a polypeptide to induce an immune response in a specific human subject, wherein the method comprises selecting an amino acid sequence that is a T-cell epitope capable of binding to at least three HLA class I molecules or at least three HLA class II molecules of the subject, and designing or preparing a polypeptide comprising the selected amino acid sequence.59.The method of claim 58, which is (a) a method for designing or preparing a polypeptide to induce a cytotoxic T lymphocyte response in a specific human subject, wherein the method comprises selecting an amino acid sequence that is a T lymphocyte epitope capable of binding to at least three subject class I HLA molecules, and designing or preparing a polypeptide comprising the selected amino acid sequence; or (b) a method for designing or preparing a polypeptide to induce a helper T lymphocyte response, wherein the method comprises selecting an amino acid sequence that is a T lymphocyte epitope capable of binding to at least three subject class II HLA molecules, and designing or preparing a polypeptide comprising the selected amino acid sequence.

60. The method of claim 58 or claim 59 further comprising administering the polypeptide to the subject.

61. A method for inducing an immune response in a subject, wherein the method comprises administering to the subject a polypeptide designed according to the method of claim 58 or claim 59.

62. A method for inducing an immune response in a specific human subject, wherein the method comprises designing or preparing a peptide according to the method of claim 58 or claim 59, and administering the peptide to the subject.

63. A system comprising (a) a storage module configured to store data comprising the HLA class I and / or class II genotype of a subject and the amino acid sequence of one or more test polypeptides; and (b) a computing module configured to identify and / or quantify the amino acid sequences in the test polypeptide(s) that are capable of binding to multiple HLA class I molecules of the subject and / or that are capable of binding to multiple HLA class II molecules of the subject.

64. The storage system of claim 63 further comprising (c) an output module configured to present (i) a prediction of whether the polypeptide(s) are immunogenic for the subject; or the sequence of one or more fragments of the polypeptides that are predicted to be immunogenic for the subject; (ii) a prediction of whether the individual will have an immune response to the administration of the one or more polypeptides or one or more pharmaceutical compositions comprising the one or more polypeptides as active ingredients; (iii) a prediction of whether the subject will have a clinical response to a method of treatment comprising administering to the subject one or more pharmaceutical compositions comprising one or more polypeptides as active ingredients; (iv) the probability that the subject will have a clinical response to the administration of one or more pharmaceutical compositions comprising the one or more polypeptides as active ingredients;(v) a prediction as to whether administration of the one or more polypeptides or one or more pharmaceutical compositions comprising the one or more polypeptides will induce a toxic immune response in the subject; (vi) a prediction that the polypeptide(s) are associated with an autoimmune disorder in the subject; (vii) a prediction as to whether the subject will have a clinical response to the administration of a checkpoint inhibitor; (viii) a recommendation as to whether or not the subject should be treated by administration of the one or more polypeptides and / or one or more pharmaceutical compositions.