POTENT MULTI-EPITOPE ANTI-CANCER VACCINE TARGETING THE AHR-ACTIVATING ENZYME INTERLEUKIN-4 INDUCED GENE 1 (IL4I1)”

Abstract

ABSTRACT “POTENT MULTI-EPITOPE ANTI-CANCER VACCINE TARGETING THE AHR-ACTIVATING ENZYME INTERLEUKIN-4 INDUCED GENE 1 (IL4I1)” The present invention relates to a potent multi-epitope cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1), a protein highly expressed in various cancers. The vaccine is designed using reverse vaccinology and immunoinformatics, incorporating cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), interferon-gamma (IFN-γ), and B-cell epitopes derived from IL4I1. This innovative approach allows the vaccine to specifically target tumor cells, inducing a robust immune response while minimizing damage to healthy tissue. It offers long-lasting immune memory, potentially preventing cancer recurrence and reducing the need for invasive treatments like surgery and radiation. By employing Explainable AI tools such as SHAP, the vaccine ensures transparency in its design and functionality. The IL4I1-based vaccine represents a novel, minimally invasive, and effective immunotherapy option, offering broad applicability across different cancer types and improving patient outcomes. Figure 1

Specification

Description:TECHNICAL FIELD
[0001] The present invention relates to the field of medical science, and more particularly, the present invention relates to the potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1).
BACKGROUND ART
[0002] The following discussion of the background of the invention is intended to facilitate an understanding of the present invention. However, it should be appreciated that the discussion is not an acknowledgment or admission that any of the material referred to was published, known, or part of the common general knowledge in any jurisdiction as of the application's priority date. The details provided herein the background if belongs to any publication is taken only as a reference for describing the problems, in general terminologies or principles or both of science and technology in the associated prior art.
[0003] Aberrant tryptophan (Trp) metabolism has been implicated as a causative and supportive factor in numerous cancers including melanomas, glioblastomas, and breast cancers. Recent studies from our own group and others have increasingly put the spotlight on another tryptophan degrading enzyme namely interleukin-4-induced gene 1 (IL4I1), which has been frequently linked with activity of the aryl hydrocarbon receptor (AHR). IL4I1 has been reported to be upregulated in tumors, which through AHR activity is detrimental to the patient by enhancing tumor survival and progression. In addition, IL4I1 has been reported to be readily presented to immune cells by MHC molecules. Therefore, this makes IL4I1 a prime candidate as a potential cancer immunotherapeutic target. In line, we have designed and developing a potent anti-cancer vaccine candidate. A multi-epitope vaccine construct was designed against the immunosuppressive IL4I1 enzyme, giving design relevance to enhance antigenic properties as well as non-toxic and non-allergenic nature using MHC and B-cell epitopes linked with suitable linkers and adjuvants. The aim of this invention is to address the current limitations of immunotherapy in cancer i.e.
- Limited effectiveness: While immunotherapy has been a breakthrough, it isn't effective for all cancers or all patients with the same cancer. Researchers are working on understanding why some patients respond well and others don't.
- Autoimmunity: Traditional immunotherapy can sometimes rev up the immune system too much, leading to immune reactions against healthy tissues. This can cause side effects ranging from mild to severe.
- High cost: Traditional immunotherapy treatments can be very expensive, limiting access for some patients.
[0004] In current oncology, a spectrum of treatment exists to combat melanoma, each with distinct mechanisms and targeted approaches. Surgical intervention, a cornerstone, involves the meticulous removal of tumors and a margin of the surrounding healthy skin. Immunotherapies, namely Pembrolizumab and Nivolumab4, harness the body's immune system to mount a robust assault on cancer cells. Targeted therapies, exemplified by Dabrafenib and Vemurafenib6, aim at specific mutations within melanoma cells, disrupting their growth. Radiation therapy employs high-energy beams to either eliminate cancer cells or alleviate associated symptoms. Interferon alpha, an immunotherapy drug, mimics natural immune proteins, contributing to the immune response against melanoma. Chemotherapy Drugs namely Dacarbazine (DTIC), Temozolomide, Nab-paclitaxelm, Paclitaxel, Cisplatin, Carboplatin to kill cancer cells throughout the body. Electro-chemotherapy merges electric fields with chemotherapy, offering localized treatment benefits. Laser therapy presents a targeted approach, obliterating small melanoma tumors using focused light. These diverse interventions offer avenues for managing cancer, showcasing a multifaceted arsenal in the ongoing battle against this malignancy.
[0005] In light of the foregoing, there is a need for Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that overcomes problems prevalent in the prior art associated with the traditionally available method or system, of the above-mentioned inventions that can be used with the presented disclosed technique with or without modification.
[0006] All publications herein are incorporated by reference to the same extent as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference. Where a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies, and the definition of that term in the reference does not apply.
OBJECTS OF THE INVENTION
[0007] The principal object of the present invention is to overcome the disadvantages of the prior art by providing Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1).
[0008] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that is Effective against a wider range of cancers than current immunotherapies that target single tumor entities as IL4I1 is expressed in a wide range of cancers including melanomas, glioblastomas, breast cancers etc.
[0009] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that is Potentially gentler on patients by targeting a specific enzyme (IL4I1) rather than the whole immune system.
[0010] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that can work strategically with existing treatments like chemo or radiation for better results.
[0011] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that are generally cheaper to manufacture than other cancer treatments.
[0012] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that offers a more convenient way to deliver cancer treatment compared to complex procedures.
[0013] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that can sometimes produce quicker immune responses than other therapies.
[0014] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that offers long-term protection against cancer recurrence.
[0015] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that prevents cancer in high-risk individuals.
[0016] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that can be tailored to target specific IL4I1 variations in different cancers.
[0017] Another object of the present invention is to provide Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1) that has fewer side effects and a more tolerable treatment experience for patients.
[0018] The foregoing and other objects of the present invention will become readily apparent upon further review of the following detailed description of the embodiments as illustrated in the accompanying drawings.
SUMMARY OF THE INVENTION
[0019] The present invention relates to Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1).
[0020] IL4I1-based vaccine represents a promising direction for overcoming limitations of current immunotherapy. This approach has the potential to address broader cancer types, reduce side effects, and can work better with existing treatments. By targeting diverse tumor antigens, cancer vaccine immunotherapy offers a dynamic approach that remains effective. Theoretically this potentially translates to sustained therapeutic benefit via both specific eradicate tumor cells.1 Unlike traditional options that require continuous administration to maintain tumor control, cancer vaccine immunotherapy has the potential to induce long-lasting immune memory.2 This could lead to significantly extended periods of remission or even cure, representing a paradigm shift in cancer treatment goals. Compared to the invasive nature of surgery or the discomfort associated with radiation therapy, cancer vaccine immunotherapy often employs minimally invasive methods like injections. This can contribute to shorter recovery times and enhanced patient comfort.
[0021] Cancers express higher levels of the AHR-activating enzyme IL4I1 (Alternative names Interleukin-4-induced protein 1, IL4-induced protein 1, hIL4I1, Protein Fig-1, hFIG1 and L-amino-acid oxidase), which is the protein synthesized by the genetic material encoded within the IL4I1 gene, which promotes tumor progression, through its effects on tumor cell motility and adaptive immunity. We have previously shown, IL4I1 expression and activity is directly proportional to the regulation of AHR. The cancer vaccine developed was made using reverse vaccinology and immunoinformatic techniques and tools to create in-silico multi-epitope peptide-based vaccine that can be used for cancer therapy. The protein's selected peptides were conjoined using the applicable adjuvants and linkers (KK, GPGPG, GPGPG and AAY). The final vaccine construct was evaluated to be stable as well as non-allergenic and immunogenic. The construct contains a large number of epitopes for cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), IFN-Y, and multiple B cell epitopes, determined by multiple bio informatics analysis.
[0022] While the invention has been described and shown with reference to the preferred embodiment, it will be apparent that variations might be possible that would fall within the scope of the present invention.
BRIEF DESCRIPTION OF DRAWINGS
[0023] So that the manner in which the above-recited features of the present invention can be understood in detail, a more particular description of the invention, briefly summarized above, may have been referred by embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only typical embodiments of this invention and are therefore not to be considered limiting of its scope, for the invention may admit to other equally effective embodiments.
[0024] These and other features, benefits, and advantages of the present invention will become apparent by reference to the following text figure, with like reference numbers referring to like structures across the views, wherein:
[0025] Figure 1: Schematic representation of the workflow for the development of IL4I1 based multi-epitope vaccine against cancer.
[0026] Figure 2: (A) 3D model of the IL4I1 based multi-epitope anti-cancer vaccine's structure. (B) Docking model of the IL4I1 based multi-epitope anti-cancer vaccine with TLR-4 of immune cells indicative that the vaccine could bind and activate immune cells.
[0027] Figure 3: (A) Plot depicts the predictive values of antibody titers targeting cancer that is expected to be generated after exposure to the IL4I1 based multi-epitope anti-cancer vaccine candidate. (B) Plot depicting the predicted immune response (in terms of cytokine production), post exposure to our IL4I1 based multi-epitope anti-cancer vaccine candidate.
[0028] Figure 4: Global population coverage analysis of our IL4I1 based multi-epitope anti-cancer vaccine candidate.
DETAILED DESCRIPTION OF THE INVENTION
[0029] While the present invention is described herein by way of example using embodiments and illustrative drawings, those skilled in the art will recognize that the invention is not limited to the embodiments of drawing or drawings described and are not intended to represent the scale of the various components. Further, some components that may form a part of the invention may not be illustrated in certain figures, for ease of illustration, and such omissions do not limit the embodiments outlined in any way. It should be understood that the drawings and the detailed description thereto are not intended to limit the invention to the particular form disclosed, but on the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the scope of the present invention as defined by the appended claim.
[0030] As used throughout this description, the word "may" is used in a permissive sense (i.e. meaning having the potential to), rather than the mandatory sense, (i.e. meaning must). Further, the words "a" or "an" mean "at least one" and the word "plurality" means "one or more" unless otherwise mentioned. Furthermore, the terminology and phraseology used herein are solely used for descriptive purposes and should not be construed as limiting in scope. Language such as "including," "comprising," "having," "containing," or "involving," and variations thereof, is intended to be broad and encompass the subject matter listed thereafter, equivalents, and additional subject matter not recited, and is not intended to exclude other additives, components, integers, or steps. Likewise, the term "comprising" is considered synonymous with the terms "including" or "containing" for applicable legal purposes. Any discussion of documents, acts, materials, devices, articles, and the like are included in the specification solely for the purpose of providing a context for the present invention. It is not suggested or represented that any or all these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention.
[0031] In this disclosure, whenever a composition or an element or a group of elements is preceded with the transitional phrase "comprising", it is understood that we also contemplate the same composition, element, or group of elements with transitional phrases "consisting of", "consisting", "selected from the group of consisting of, "including", or "is" preceding the recitation of the composition, element or group of elements and vice versa.
[0032] The present invention is described hereinafter by various embodiments with reference to the accompanying drawing, wherein reference numerals used in the accompanying drawing correspond to the like elements throughout the description. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiment set forth herein. Rather, the embodiment is provided so that this disclosure will be thorough and complete and will fully convey the scope of the invention to those skilled in the art. In the following detailed description, numeric values and ranges are provided for various aspects of the implementations described. These values and ranges are to be treated as examples only and are not intended to limit the scope of the claims. In addition, several materials are identified as suitable for various facets of the implementations. These materials are to be treated as exemplary and are not intended to limit the scope of the invention.
[0033] The present invention relates to Potent multi-epitope anti-cancer vaccine targeting the AHR-activating enzyme Interleukin-4 induced gene 1 (IL4I1).
[0034] IL4I1-based vaccine represents a promising direction for overcoming limitations of current immunotherapy. This approach has the potential to address broader cancer types, reduce side effects, and can work better with existing treatments. By targeting diverse tumor antigens, cancer vaccine immunotherapy offers a dynamic approach that remains effective. Theoretically this potentially translates to sustained therapeutic benefit via both specific eradicate tumor cells.1 Unlike traditional options that require continuous administration to maintain tumor control, cancer vaccine immunotherapy has the potential to induce long-lasting immune memory.2 This could lead to significantly extended periods of remission or even cure, representing a paradigm shift in cancer treatment goals. Compared to the invasive nature of surgery or the discomfort associated with radiation therapy, cancer vaccine immunotherapy often employs minimally invasive methods like injections. This can contribute to shorter recovery times and enhanced patient comfort.
[0035] Cancers express higher levels of the AHR-activating enzyme IL4I1 (Alternative names Interleukin-4-induced protein 1, IL4-induced protein 1, hIL4I1, Protein Fig-1, hFIG1 and L-amino-acid oxidase), which is the protein synthesized by the genetic material encoded within the IL4I1 gene, which promotes tumor progression, through its effects on tumor cell motility and adaptive immunity. We have previously shown, IL4I1 expression and activity is directly proportional to the regulation of AHR. The cancer vaccine developed was made using reverse vaccinology and immunoinformatic techniques and tools to create in-silico multi-epitope peptide-based vaccine that can be used for cancer therapy. The protein's selected peptides were conjoined using the applicable adjuvants and linkers (KK, GPGPG, GPGPG and AAY). The final vaccine construct was evaluated to be stable as well as non-allergenic and immunogenic. The construct contains a large number of epitopes for cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), IFN-Y, and multiple B cell epitopes, determined by multiple bio informatics analysis.
[0036] Our vaccine has CTL ['LALDDVAAL', 'FYLSFAEAL', and 'YPPPREGAL']; HTL ['GFFYLSFAEALRAHS', 'DGFFYLSFAEALRAH', and 'EDGFFYLSFAEALRA']; IFN ['SEDGFFYLSFAEALR', 'MSEDGFFYLSFAEAL' and 'VMSEDGFFYLSFAEA'] and B cells ['TWTEVHEVKLRNYVVE', 'KFTQYDKNTWTEVHEV' and 'YEQLLKVVTWGLNRTL'] peptide components derived from the protein of IL4I1 gene. This gene has never been used as a basis for a cancer vaccine before. This differentiates our vaccine from other same cancer type vaccine currently available in the market.
[0037] Chemotherapy remains a cornerstone of cancer treatment, but cancer vaccines offer several potential advantages. Targets tumor antigens: Cancer vaccines target specific antigens on cancer cells, minimizing harm to healthy cells compared to chemotherapy's systemic attack on rapidly dividing cells, reducing side effects like nausea, hair loss, etc. Tumors can develop resistance to chemotherapy drugs, rendering them ineffective. Cancer vaccines, targeting diverse tumor antigens, are less susceptible to this phenomenon. They may induce long-lasting immune memory, reducing the risk of cancer recurrence after initial treatment and hence potentially maintaining long-term efficacy. Unlike chemotherapy's intravenous or oral administration, most cancer vaccines are administered through injections potentially reducing patient discomfort and associated risks.
[0038] While surgery remains a critical tool for cancer treatment but unlike surgery which requires incisions and tissue removal, most cancer vaccines are administered through injections reducing patient discomfort, recovery time, and associated risks like infection. Certain cancer vaccines may induce long-lasting immune memory, potentially preventing cancer recurrence and offering a potential cure compared to surgery's focus on removing existing tumors. Unlike surgery, which may damage nearby healthy tissue along with the tumor, cancer vaccines target specific tumor antigens, minimizing damage to surrounding healthy cells. While surgery often requires repeat procedures depending on tumor recurrence, cancer vaccines with lasting immune activation may reduce the need for repeated interventions and associated risks.
[0039] While radiation therapy plays a crucial role in cancer treatment but unlike radiation's broad-spectrum of second cancers18, cancer vaccines specifically target tumor antigens, minimizing harm to healthy cells and may induce long-lasting immune memory, reducing the risk of cancer recurrence after initial treatment. Tumors can develop resistance to radiation over time, rendering it ineffective. Cancer vaccines, targeting diverse tumor antigens, are less susceptible to this phenomenon, potentially maintaining long-term efficacy. Unlike radiation therapy requiring external or internal beam exposure, most cancer vaccines are administered through injections, reducing patient discomfort and associated risks.
[0040] Various modifications to these embodiments are apparent to those skilled in the art from the description and the accompanying drawings. The principles associated with the various embodiments described herein may be applied to other embodiments. Therefore, the description is not intended to be limited to the 5 embodiments shown along with the accompanying drawings but is to be providing the broadest scope consistent with the principles and the novel and inventive features disclosed or suggested herein. Accordingly, the invention is anticipated to hold on to all other such alternatives, modifications, and variations that fall within the scope of the present invention and appended claims. , Claims:CLAIMS
We Claim:
1) A multi-epitope cancer vaccine, the vaccine comprising:
Peptides derived from the Interleukin-4 induced gene 1 (IL4I1) protein, targeting cancer cells expressing high levels of IL4I1;
Cytotoxic T lymphocyte (CTL) epitopes, including 'LALDDVAAL,' 'FYLSFAEAL,' and 'YPPPREGAL,' capable of eliciting an immune response to destroy tumor cells;
Helper T lymphocyte (HTL) epitopes, including 'GFFYLSFAEALRAHS,' 'DGFFYLSFAEALRAH,' and 'EDGFFYLSFAEALRA,' that support the immune system's recognition and elimination of cancer cells;
Interferon-gamma (IFN-γ) inducing epitopes, such as 'SEDGFFYLSFAEALR,' 'MSEDGFFYLSFAEAL,' and 'VMSEDGFFYLSFAEA,' designed to enhance immune signaling against tumor cells; and
B-cell epitopes, including 'TWTEVHEVKLRNYVVE,' 'KFTQYDKNTWTEVHEV,' and 'YEQLLKVVTWGLNRTL,' for generating a humoral immune response.
2) The cancer vaccine as claimed in claim 1, wherein the peptides are conjoined using linkers selected from the group comprising KK, GPGPG, and AAY linkers to enhance the stability and immunogenicity of the vaccine construct.
3) The cancer vaccine as claimed in claim 1, wherein the vaccine further comprising an adjuvant selected to enhance the immune response, wherein the adjuvant is combined with the multi-epitope peptide structure for improved immunogenicity.
4) A method for treating cancer in a subject, comprising administering the multi-epitope vaccine of claim 1 to elicit a sustained immune response targeting cancer cells expressing IL4I1.
5) The method as claimed in claim 4, wherein the vaccine is administered via injection, offering a minimally invasive alternative to conventional cancer treatments.
6) The cancer vaccine as claimed in claim 1, wherein the vaccine induces long-lasting immune memory, reducing the likelihood of cancer recurrence after the initial treatment.
7) A system for developing a multi-epitope cancer vaccine, the system comprising:
the use of reverse vaccinology techniques to identify and design immunogenic peptides from IL4I1.
immunoinformatics tools to predict and select CTL, HTL, IFN-γ, and B-cell epitopes from the IL4I1 protein.
computational tools to evaluate the vaccine construct for stability, non-allergenicity, and immunogenicity.

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