INO-5401

Significant progress toward submitting a biologics license application (BLA) for INO-3107 as a potential treatment for recurrent respiratory papillomatosis (RRP) Resolved previously announced manufacturing issue concerning the single-use array component of the CELLECTRA device and completed drafting of all non-device BLA modules On track to begin rolling submission of BLA in mid-2025 and to request priority review with goal of completing the submission in the second half of 2025 and receiving acceptance of the submission by end of the year Announced durability data from retrospective study showing that 50% of patients achieved a Complete Response in the second 12-month period (year 2) with 86% of patients showing a reduction in surgery of 50% or greater in year 2; data to be included in BLA submission Announced promising interim results from ongoing proof-of-concept Phase 1 trial showing DNA-encoded monoclonal antibodies (DMAb) targeting COVID-19 were well tolerated and exhibited long-lasting in vivo production DMAb technology has the potential to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses, making it a potentially promising platform for a broad range of diseases DNA Medicine technology has the potential to provide long term production of therapeutic antibodies and deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins Resolved previously announced manufacturing issue concerning the single-use array component of the CELLECTRA device and completed drafting of all non-device BLA modules On track to begin rolling submission of BLA in mid-2025 and to request priority review with goal of completing the submission in the second half of 2025 and receiving acceptance of the submission by end of the year Announced durability data from retrospective study showing that 50% of patients achieved a Complete Response in the second 12-month period (year 2) with 86% of patients showing a reduction in surgery of 50% or greater in year 2; data to be included in BLA submission DMAb technology has the potential to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses, making it a potentially promising platform for a broad range of diseases DNA Medicine technology has the potential to provide long term production of therapeutic antibodies and deliver a broad spectrum of therapeutic proteins that could be used to treat diseases with missing or defective proteins PLYMOUTH MEETING, Pa., March 18, 2025 /PRNewswire/ -- INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced its financial results and operational highlights for the fourth quarter and full year ended December 31, 2024 and provided a business update and description of operational highlights during the year. "INOVIO's recent progress puts us on the cusp of achieving several long-term goals for our DNA medicines, most importantly the submission of our first BLA and potential transition to a commercial-stage company," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "By resolving the previously announced device array component issue, we are back on track to submitting our first BLA for INO-3107 to the FDA. We anticipate starting our submission in mid-2025 with non-device related modules under the agency's rolling submission program, assuming it is granted, with the goal of having the complete submission accepted for priority review before the end of the year. We continue to believe that INO-3107 has the potential to be the preferred product candidate offering durable clinical benefit, tolerability and a patient-centric dosing regimen and are moving forward with urgency." Dr. Michael Sumner, INOVIO's Chief Medical Officer, said, "While delivering INO-3107 to patients remains our primary focus, we are extremely pleased with recently announced data from a proof-of-concept trial with our DMAb technology that showed durable in vivo antibody production. DMAbs represent a potential breakthrough as they have the ability to overcome traditional monoclonal antibody production challenges, such as short half-life and anti-drug immune responses. They have the potential to transform treatments for infectious diseases, as well as cancer and metabolic disorders by enabling long-term production of therapeutic antibodies and other proteins. Unlike other delivery platforms, our DNA-based approach has demonstrated sustained antibody production without generating anti-drug antibodies, making it a potentially promising long-term solution for conditions requiring continuous therapeutic protein delivery. We look forward to continuing to advance this technology and other promising pipeline candidates through collaborations and other potential strategic opportunities." Operational Highlights INO-3107 – Recurrent Respiratory Papillomatosis (RRP) Made significant progress toward submitting the BLA by completing the drafting of all non-device modules and resolving the previously announced manufacturing issue involving the single-use array component of the CELLECTRA device and enabling the final step of FDA-required device verification (DV) testing. Reported data from a retrospective trial (RRP-002) showing that patients continued to improve into years two and three following their initial dosing regimen when compared to their response at Week 52. In the trial, one-half of RRP patients treated with INO-3107 achieved a complete response (CR) and required no surgery in the second 12-month period when evaluated at the end of year two. Published and presented the full safety and efficacy data for the Phase 1/2 trial, as well as new immunology data demonstrating the ability of INO-3107 to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of those T cells into airway tissues and papilloma of RRP patients, which could potentially slow or eliminate papilloma regrowth. This data was published in Nature Communications in February 2025. The European Medicines Agency's Committee for Advanced Therapies (CAT) certified the quality and non-clinical data for INO-3107, confirming that CMC data and nonclinical results available to date comply with the scientific and technical standards to be used in evaluating a potential European Marketing Authorization Application. INO-3107 was designated an innovative medicine as part of the U.K.'s Innovative Licensing and Access Pathway (ILAP). Progressed commercial readiness plans, including refining go-to-market strategy focused on patient and physician needs; driving key strategic decisions on pricing and access, product distribution, targeting and segmentation, and product positioning; and developing plans for the build out of the commercial organization. Next Steps: Complete FDA-required design-verification testing - anticipated to be complete in first half of 2025. Update IND and initiate confirmatory trial. Submit BLA to the FDA – anticipate beginning rolling submission process mid-2025 and requesting priority review with goal of completing submission in second half of 2025 and receiving FDA acceptance of submission by year end. Submit a long-term study protocol to the FDA following BLA submission. Present and publish clinical, immunology and durability data at targeted scientific and medical conferences in 2025. INO-3112 - Oropharyngeal Squamous Cell Carcinoma (OPSCC) Advanced development plans for a Phase 3 trial for INO-3112 in combination with LOQTORZI® (toripalimab-tpzi), a recently approved PD-1 inhibitor in the U.S. and Europe. Gained alignment with FDA on the planned Phase 3 trial design and received initial feedback from European regulatory authorities on proposed trial design. Entered into a clinical collaboration and supply agreement with Coherus BioSciences, Inc. for the use of LOQTORZI in the trial. Next Steps: Finalize protocol of the Phase 3 trial in consultation with the FDA. INOVIO anticipates it will conduct the trial in North America and Europe in patients with locoregionally advanced, high-risk, HPV16/18-positive OPSCC. Complete ongoing manufacture of drug supply for trial. Other Pipeline Updates Top-line interim results were announced from an ongoing Phase 1 proof-of-concept trial evaluating DMAbs targeting COVID-19. In the trial, 100% (24/24) of participants who reached week 72 maintained biologically relevant levels of DMAbs, confirming the durability of in vivo antibody production. Notably, no participant developed anti-drug antibodies, a common challenge observed in other gene-based delivery platforms, such as adeno-associated virus mediated antibody expression. Additionally, the DMAbs were well tolerated in the trial, with the most common side effects being mild, temporary injection site reactions, such as pain and redness. The trial is being led by The Wistar Institute in collaboration with INOVIO, AstraZeneca, and the University of Pennsylvania and funded by the Defense Advanced Research Projects Agency (DARPA) and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND). INOVIO and its partners anticipate additional data to be presented at upcoming scientific conferences and published in a peer-reviewed journal. Advanced development plans for a Phase 2 trial for INO-4201 as a potential booster to ERVEBO® (rVSV-ZEBOV), including gaining alignment with FDA on the trial's protocol and path to potential approval. In 2025, the company anticipates finalizing the trial protocols and seeking funding to support trial activities. INOVIO also plans to submit the data from its completed Phase 1b trial to a peer-reviewed publication for publication, including FANG assay data indicating that boosting with INO-4201 can elicit neutralizing antibody response comparable to that achieved by ERVEBO, an approved primary series vaccination against Ebola. Continued efforts to move INO-5401 into its next stage of development for glioblastoma (GBM), which the company believes will be a controlled Phase 2 trial. INOVIO plans on completing manufacture of drug supply for the next trial during 2025. The Basser Center at the University of Pennsylvania continues evaluating the tolerability and immunogenicity of INO-5401 in a fully enrolled Phase 1 study exploring the potential to prevent cancer in people with BRCA1 or BRCA2 mutations. INOVIO's collaborator, ApolloBio, continues recruitment into its Phase 3 trial evaluating INO-3100 as a potential treatment for HPV 16/18 positive cervical dysplasia in China. Operational and Financial Updates Announced appointment of Steven Egge as Chief Commercial Officer in July 2024. Mr. Egge has broad commercial and therapeutic area experience, including in HPV-related diseases and cancers, vaccines and rare diseases, and has overseen or contributed to more than a dozen commercial product launches throughout his career. Raised over $72 million in gross proceeds from ATM and two offerings of equity securities in April and December 2024. 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: As of December 31, 2024, cash, cash equivalents and short-term investments were $94.1 million compared to $145.3 million as of December 31, 2023. Revenues: Total revenues were $117,000 and $218,000 for the quarter and year ended December 31, 2024, respectively, compared to $103,000 and $832,000 for the same periods in 2023. Research and Development (R&D) Expenses: R&D expenses for the quarter and year ended December 31, 2024 were $12.9 million and $75.6 million, respectively, compared to $17.3 million and $86.7 million for the same periods in 2023. The decrease in R&D expenses was primarily the result of lower employee and consultant compensation, including stock-based compensation, lower drug manufacturing and clinical trial expenses related to INO-4800, partially offset by an increase in drug manufacturing costs related to INO-3107 and higher engineering professional and outside services related to device development, among other variances. General and Administrative (G&A) Expenses: G&A expenses were $7.6 million and $37.0 million, respectively, for the quarter and year ended December 31, 2024, versus $10.2 million and $47.6 million, respectively, for the same periods in 2023. The decrease in G&A expenses was primarily related to a decrease in employee compensation, including stock-based compensation, and a decrease in legal expenses, among other variances. Total Operating Expenses: Total operating expenses were $20.5 million and $112.6 million for the quarter and year ended December 31, 2024, respectively, compared to $27.5 million and $144.8 million for the same period in 2023. Net Loss: INOVIO's net loss for the quarter and year ended December 31, 2024 was $19.4 million, or $0.65 per basic and diluted share, and $107.3 million, or $3.95 per basic and diluted share, respectively, compared to net loss of $25.0 million, or $1.10 per basic and diluted share, and $135.1 million, or $6.09 per basic and diluted share, for the quarter and year ended December 31, 2023, respectively. Shares Outstanding: As of December 31, 2024, INOVIO had 36.1 million common shares outstanding and 50.0 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting, and conversion, as applicable, of its outstanding common stock warrants, pre-funded warrants, stock options, restricted stock units and convertible preferred stock. INOVIO's balance sheet and statement of operations are provided below. Additional information is included in INOVIO's annual report on Form 10-K for the year ended December 31, 2024, which can be accessed at: http://ir.inovio.com/financials/default.aspx. Cash Guidance INOVIO estimates its current cash, cash equivalents and short-term investments balances to support the company's operations into the first quarter of 2026. This projection includes an operational net cash burn estimate of approximately $27 million for the first quarter of 2025. These cash runway projections do not include any further capital-raising activities that INOVIO may undertake. Conference Call / Webcast Information INOVIO's management will host a live conference call and webcast with slides at 4:30 p.m. ET today to discuss INOVIO's financial results and provide a general business update. The live webcast and replay may be accessed by visiting INOVIO's website at http://ir.inovio.com/events-and-presentations/default.aspx. About INOVIO's DNA Medicines Platform INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms. About INOVIO INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com. Forward-Looking Statements This press release contains certain forward-looking statements relating to our business, including the planned initiation and conduct of pre-clinical studies and clinical trials and the availability and timing of data from those studies and trials, the completion of the FDA-required device verification testing, the planned submission of a BLA in mid-2025 and request for priority review and goal of FDA's acceptance of the submission by the end of 2025, the potential commercial launch of INO-3107 if regulatory approval is obtained, the potential benefits of our product candidates and the expected sufficiency of our cash resources into the first quarter of 2026. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2024 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law. Contacts Media: Jennie Willson, (267) 429-8567, communications@inovio.com Investors: Peter Vozzo, ICR Healthcare, 443-213-0505, investor.relations@inovio.com Inovio Pharmaceuticals, Inc. CONSOLIDATED BALANCE SHEETS December 31, 2024 2023 ASSETS Current assets: Cash and cash equivalents $65,813,297 $14,310,862 Short-term investments 28,300,232 130,982,913 Accounts receivable from affiliated entities 1,199,056 2,405,228 Prepaid expenses and other current assets, including with affiliated entity 2,517,465 5,414,097 Total current assets 97,830,050 153,113,100 Fixed assets, net 3,659,818 4,960,986 Investments in affiliated entity 1,613,844 2,780,287 Operating lease right-of-use assets 8,113,840 9,491,735 Other assets 1,979,654 605,315 Total assets $113,197,206 $170,951,423 LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable and accrued expenses $16,200,013 $19,847,744 Accounts payable and accrued expenses due to affiliated entities 1,351,163 1,070,519 Accrued clinical trial expenses 2,021,860 2,365,382 Common stock warrant liability 13,255,188 — Operating lease liability 2,497,360 2,406,522 Grant funding liability, including from affiliated entity — 109,407 Convertible senior notes — 16,770,654 Total current liabilities 35,325,584 42,570,228 Operating lease liability, net of current portion 9,367,827 11,032,066 Total liabilities 44,693,411 53,602,294 Commitments and contingencies Inovio Pharmaceuticals, Inc. stockholders' equity: Preferred stock—par value $0.001; Authorized shares: 10,000,000, issued and outstanding shares: 9 at December 31, 2024 and 2023 — — Common stock—par value $0.001; Authorized shares: 600,000,000 at December 31, 2024 and 2023, issued and outstanding: 36,099,991 at December 31, 2024 and 22,793,075 at December 31, 2023 36,099 22,792 Additional paid-in capital 1,799,362,625 1,740,954,074 Accumulated deficit (1,730,219,262) (1,622,965,136) Accumulated other comprehensive loss (675,667) (662,601) Total Inovio Pharmaceuticals, Inc. stockholders' equity 68,503,795 117,349,129 Total liabilities and stockholders' equity $113,197,206 $170,951,423 Inovio Pharmaceuticals, Inc. CONSOLIDATED STATEMENTS OF OPERATIONS For the Year ended December 31, 2024 2023 Revenue from collaborative arrangements and other contracts, including affiliated entity $217,756 $832,010 Operating expenses: Research and development 75,620,340 86,676,563 General and administrative 36,996,338 47,582,104 Impairment of goodwill — 10,513,371 Total operating expenses 112,616,678 144,772,038 Loss from operations (112,398,922) (143,940,028) Other income (expense): Interest income 4,766,993 8,133,290 Interest expense (177,833) (1,222,789) Change in fair value of common stock warrant liability 2,808,608 — (Loss) gain on investment in affiliated entity (1,166,443) 773,145 Net unrealized gain on available-for-sale equity securities 2,077,182 5,850,626 Other expense, net (3,163,711) (4,711,596) Net loss $(107,254,126) $(135,117,352) Net loss per share Basic and diluted $(3.95) $(6.09) Weighted average number of common shares outstanding Basic and diluted 27,160,863 22,173,662 View original content to download multimedia:https://www.prnewswire.com/news-releases/inovio-reports-fourth-quarter-and-full-year-2024-financial-results-and-operational-highlights-302405001.html SOURCE INOVIO Pharmaceuticals, Inc.

癌症疫苗是生物技术在肿瘤学领域中日益重要的一个方向，它利用人体免疫系统来对抗癌细胞。癌症疫苗大致可分为两类：预防性疫苗和治疗性疫苗。 预防性疫苗旨在通过预防可能致癌的感染来防止癌症发生。人乳头瘤病毒（HPV）疫苗，如人乳头瘤病毒重组蛋白疫苗（Gardasil）和希瑞适（Cervaris），可预防导致宫颈癌、肛门癌和其他癌症的 HPV 毒株。 治疗性疫苗则是给已确诊癌症的患者使用。其目的是刺激免疫系统识别并攻击癌细胞。这些疫苗通常针对肿瘤相关抗原或患者特异性新抗原，训练免疫系统识别并摧毁恶性细胞。 癌症疫苗的开发涉及多种技术。在本文中，我们将概述疫苗如何成为攻克癌症的有效手段。 癌症疫苗及其多样的研发路径除了预防性和治疗性疫苗的区别外，癌症疫苗的研发还涉及许多不同的技术。肿瘤学涵盖了各种各样的肿瘤，对于黑色素瘤，mRNA 技术或许是有效的研发方向，但其他肿瘤对其反应可能不同。 mRNA 癌症疫苗：mRNA 疫苗将编码肿瘤特异性抗原的合成信使 RNA 输送到人体细胞内。这些细胞随后会产生抗原，促使免疫系统识别并攻击表达这些抗原的癌细胞。mRNA 疫苗通常针对新抗原（仅存在于肿瘤细胞中的独特突变），以引发特异性免疫反应。比如 Moderna 和默克公司的 mRNA - 4157/V940，这是一种个性化疫苗，最多可编码 34 种根据个体肿瘤特征定制的新抗原。它与帕博利珠单抗（Keytruda）联合使用，在 2b 期临床试验中，对黑色素瘤患者显示出良好的效果，降低了癌症复发风险。两家公司已于 2024 年 10 月启动了 3 期临床试验。另一个例子是 BioNTech 的 BNT111，自新冠疫情以来，BioNTech 在 mRNA 领域颇负盛名。BNT111 也专注于黑色素瘤治疗，最近达到了其 2 期临床试验的主要终点。mRNA 疫苗具有研发迅速和可定制的特点，能灵活针对多种癌症。它们已显示出强大的免疫原性和良好的安全性。不过，确保高效地将疫苗输送到靶细胞并实现持续的抗原表达仍是有待克服的难题。此外，肿瘤的高突变率也增加了合适抗原识别的难度。 DNA 癌症疫苗：DNA 疫苗将编码肿瘤抗原的质粒 DNA 导入宿主细胞，从而产生抗原并激活免疫系统。DNA 通过肌肉注射或皮内注射等多种方式导入人体。像电穿孔这样的先进技术，常被用于增强细胞对 DNA 的摄取，它利用短电脉冲使细胞膜更具渗透性。由 Nykode 和基因泰克（Genentech）共同开发的 VB10.NEO，可针对多达 20 种新抗原，目前正在进行针对实体瘤的 2 期试验。由于基因泰克决定终止合作，Nykode 将于 2025 年 1 月重新获得该候选疫苗的独家控制权。据 Nykode 称，基因泰克的终止通知 “未提及临床数据或与技术平台相关的内容”。Inovio Pharmaceuticals 也在开发 DNA 癌症疫苗，INO - 5401 目前正在针对携带 BRCA1 或 BRCA2 突变的癌症患者进行 1 期试验。DNA 疫苗稳定性好，可长期储存，还能编码多种抗原，有助于引发广泛的免疫反应。但和 mRNA 疫苗一样，高效递送仍是其面临的挑战。从理论上讲，它还存在整合到宿主基因组的风险，这就需要在设计和测试时格外谨慎。 基于肽的癌症疫苗：这类疫苗将与肿瘤相关抗原（TAAs）或肿瘤特异性抗原（TSAs）对应的特定肽引入人体。抗原呈递细胞（APCs），如树突状细胞，会处理这些肽，并通过主要组织相容性复合体（MHC）分子将其呈现在细胞表面。这一过程会激活细胞毒性 T 淋巴细胞（CTLs）和辅助性 T 细胞，从而引发针对表达这些抗原的肿瘤细胞的靶向免疫反应。Immatics 公司为肾细胞癌开发的 IMA901 就是这类疫苗的一个例子。尽管它在早期显示出有希望的结果，并进入了 3 期临床试验，但最终未达到试验终点，未能获批。不过，还有其他有潜力的候选疫苗正在研发中。Mimivax 公司的 SurVaxM 目前正在进行多项临床试验，最初聚焦于胶质母细胞瘤，且已完成针对该适应症的 2 期研究。它针对的是存活素，这是一种在 95% 的胶质母细胞瘤和其他癌症中都存在的细胞存活蛋白。虽然基于肽的疫苗在肿瘤学领域尚未产生重大突破，但它们在实验性治疗中仍发挥着作用。目前的研究重点已转向将肽作为联合治疗策略的一部分，并利用新一代平台，如新抗原疫苗。该领域仍处于实验阶段，但在特定的细分应用或作为辅助治疗方面颇具前景。 病毒载体癌症疫苗：这类疫苗利用经过改造的病毒作为载体，将编码肿瘤抗原的遗传物质输送到宿主细胞中。感染宿主细胞后，病毒载体导入遗传物质，使宿主细胞表达肿瘤抗原。抗原的呈递会激活免疫系统，尤其是细胞毒性 T 淋巴细胞，使其识别并摧毁表达这些抗原的癌细胞。2015 年，安进公司的 T - VEC（Imlygic）获得美国食品药品监督管理局（FDA）批准，用于治疗转移性黑色素瘤。T - VEC 是一种经过工程改造的溶瘤单纯疱疹病毒 1 型（HSV - 1），它能在肿瘤细胞内选择性复制并裂解肿瘤细胞，同时表达粒细胞 - 巨噬细胞集落刺激因子（GM - CSF），以增强全身抗肿瘤免疫力。尽管在免疫功能低下的患者中，病毒载体疫苗存在病毒不受控制复制或引发不良免疫反应的风险，但它仍然是癌症疫苗开发的重点领域，目前的研究致力于提高其疗效和安全性。 基于细胞的癌症疫苗：基于细胞的疫苗是癌症免疫疗法中一种前景广阔且已取得成果的方法，它利用全细胞（自体或异体来源）来呈递肿瘤抗原，刺激靶向免疫反应。主要有两种类型：树突状细胞疫苗和全肿瘤细胞疫苗。树突状细胞（DCs）是抗原呈递细胞，从患者体内采集后，在体外加载肿瘤相关抗原，然后再回输到患者体内，旨在激活 T 细胞靶向并清除肿瘤细胞。全肿瘤细胞疫苗则使用经过辐照处理的肿瘤细胞，这些细胞经过工程改造后可分泌免疫刺激因子，如粒细胞 - 巨噬细胞集落刺激因子（GM - CSF），以增强对癌细胞的免疫反应。Dendreon 公司开发的 Sipuleucel - T（Provenge）是 FDA 批准的首个用于转移性去势抵抗性前列腺癌的自体树突状细胞疫苗。该疫苗采集患者的外周血单个核细胞，使其接触结合了前列腺酸性磷酸酶（PAP）和 GM - CSF 的融合蛋白（PA2024），激活后的细胞再回输到患者体内，旨在引发针对表达 PAP 的前列腺癌细胞的 T 细胞介导的免疫反应。不过，Dendreon 公司后来申请破产，Provenge 目前由三胞集团持有并继续供应。另一个候选疫苗是 Aduro Biotech 公司的 GVAX，它由经过基因改造、可分泌 GM - CSF 的辐照肿瘤细胞组成，能增强抗原呈递并刺激免疫反应。GVAX 的多种变体已针对多种癌症进行了研究，包括胰腺癌。最近的研究探索了将 GVAX 与免疫检查点抑制剂联合使用，以提高疗效。 挑战中前行，癌症疫苗前景光明开发癌症疫苗面临多方面的挑战。癌症在患者之间以及单个肿瘤内部都表现出显著的基因多样性，这使得确定通用的疫苗靶点变得复杂。这种多样性需要个性化的方法，才能有效地针对每个肿瘤独特的抗原情况。 肿瘤微环境（TME）的免疫抑制特性是另一个重大挑战。肿瘤微环境常常抑制免疫反应，使肿瘤细胞能够逃避免疫系统的检测。克服这种免疫抑制环境对癌症疫苗的疗效至关重要。 一些研发方法还需要大量资源。值得庆幸的是，肿瘤学仍然是生物技术领域吸引投资最多的领域之一。2024 年，癌症疫苗市场价值 121.4 亿美元，预计将以 17% 的复合年增长率增长，到 2032 年达到 425.8 亿美元。相比之下，更广泛的肿瘤治疗市场也在扩张，但复合年增长率略低。例如，全球肿瘤市场预计在 2023 年至 2028 年间，复合年增长率约为 12.0%。 此外，肿瘤免疫治疗（IO）领域在不断发展，癌症疫苗发挥着关键作用。2022 年，涉及癌症疫苗的临床试验数量增长了 17.4%。这得益于该领域有前景的创新成果，以及像 mRNA 这样的一些递送系统多年来积累的可信度。 人工智能（AI）在未来的癌症疫苗开发中也可能发挥重要作用。利用 AI 和机器学习有助于快速准确地预测新抗原，简化个性化疫苗的开发过程。 疫苗在联合治疗方面也有很大潜力。将癌症疫苗与免疫检查点抑制剂（如帕博利珠单抗）结合使用，已显示出增强的抗肿瘤反应，表明联合治疗具有协同潜力。 此外，针对各种癌症的疫苗研究正在不断拓展，包括像胰腺癌和胶质母细胞瘤等传统上治疗难度较大的癌症。目前，人们也在努力开发针对致癌病毒和高危人群的预防性疫苗。 原文来源：The rise of cancer vaccines: A new era in immunotherapy 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观，不代表本站立。