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溶瘤治疗：让病毒和细菌变成抗癌工具，这条路到底怎么走？ 很多人第一次听到“溶瘤病毒”或“溶瘤菌”，第一反应大概是： 病毒、细菌不是会让人生病吗？怎么还能拿来治癌？ 这个问题问得很对。 溶瘤治疗的核心，不是把普通病毒、普通细菌直接打进人体，而是利用它们某些天然特性，再经过筛选、减毒或基因工程改造，让它们更偏向肿瘤环境，并把肿瘤从“免疫系统看不清的地方”，变成“免疫系统必须处理的现场”。 如果用一个不太严肃但好懂的比喻： 传统化疗像是大范围轰炸；靶向药像是瞄准某个关键零件；PD-1 这类免疫治疗像是解除免疫刹车。 而溶瘤治疗更像是把一个“引爆器”送进肿瘤内部：一方面直接破坏肿瘤细胞，另一方面把肿瘤里的抗原、炎症信号和免疫细胞都调动起来。 它真正有意思的地方，不只是“把肿瘤细胞杀死”，而是把一次局部破坏，尽量变成一次全身抗肿瘤免疫动员。 快读要点 溶瘤治疗不是“病毒或细菌神奇吃掉癌症”，而是利用微生物的复制、定位和免疫刺激能力，改造肿瘤局部环境。 溶瘤病毒更像进入肿瘤细胞内部的“复制型武器”；细菌路线更强调肿瘤定位、局部免疫激活和工程化递送。 T-VEC 是代表性溶瘤病毒产品；BCG 膀胱灌注则是细菌参与抗肿瘤免疫治疗最成熟的现实样板。 已上市产品包括 Imlygic/T-VEC、Oncorine/H101、Delytact/G47Δ，以及膀胱癌场景中的 TICE BCG。 这条路线未来更可能作为“肿瘤免疫点火器”，与免疫检查点抑制剂、放疗、化疗、细胞治疗等组合使用。 一、溶瘤治疗不是一条路线，而是一组路线 大体上，可以分成两类。 第一类是溶瘤病毒。 它们通常来自疱疹病毒、腺病毒、痘苗病毒、呼肠孤病毒、柯萨奇病毒等。经过改造后，病毒更容易在肿瘤细胞里复制，而在正常组织里复制能力受到限制。 病毒进入肿瘤细胞后，会利用细胞资源复制自己，最后让肿瘤细胞裂解。细胞一裂，肿瘤抗原、病毒成分和危险信号就一起释放出来，免疫系统被迫注意到这个原本“装死”的肿瘤。 第二类可以宽泛叫细菌疗法，或者更准确地说，肿瘤靶向细菌/细菌免疫治疗。 有些细菌天然喜欢低氧、坏死、免疫抑制的肿瘤微环境；有些细菌可以被工程化，携带细胞因子、毒素片段或免疫调节分子。 它们未必都像病毒那样直接把肿瘤细胞“撑爆”，更多时候是把肿瘤局部变成一个免疫炎症现场。 所以，“溶瘤菌”这个词可以用于科普，但专业一点讲，它包含了细菌介导的肿瘤定位、局部免疫激活和工程化递送，并不都等同于直接裂解肿瘤。 二、溶瘤病毒的代表案例：T-VEC 如果要找一个最适合普通读者理解的溶瘤病毒案例，T-VEC 是绕不开的。 T-VEC，全名 talimogene laherparepvec，商品名 Imlygic。它是基于 1 型单纯疱疹病毒，也就是 HSV-1 改造而来的溶瘤病毒，主要用于部分不可手术切除、可以直接注射病灶的黑色素瘤。 T-VEC溶瘤病毒机制图 它的设计逻辑可以拆成三步。 第一步，瘤内注射。 T-VEC 不是像普通输液那样全身给药，而是直接打进可见或可触及的肿瘤病灶里。这样做的好处是让病毒优先到达肿瘤现场，同时降低全身暴露。 第二步，选择性复制并裂解肿瘤细胞。 T-VEC 删除了 HSV-1 中与正常细胞复制能力相关的关键基因，例如 ICP34.5。简单说，正常细胞遇到病毒会启动防御反应，而许多肿瘤细胞这套防御已经坏掉了，所以改造后的病毒更容易在肿瘤细胞里复制。 病毒复制到一定程度，肿瘤细胞会裂解，释放出新的病毒颗粒和肿瘤抗原。 第三步，激活免疫系统。 T-VEC 还加入了 GM-CSF 这个免疫刺激因子。它的作用可以理解为“喊人”：吸引并激活树突状细胞，让它们把肿瘤抗原呈递给 T 细胞。 于是，治疗目标就不只是被注射的那个肿瘤结节，而是希望诱导更广泛的抗肿瘤免疫反应。 所以，T-VEC 不是简单的“病毒吃肿瘤”。更准确地说，它是“局部病毒复制 + 肿瘤裂解 + 免疫激活”的组合方案。 三、细菌路线的主流案例：BCG 膀胱灌注 如果讲细菌治疗，最成熟、最有临床存在感的例子不是某个很新的工程菌，而是一个老朋友：BCG。 BCG 本来是卡介苗，也就是减毒牛型结核分枝杆菌。它最出名的身份是疫苗，但在肿瘤治疗里，它还有另一个重要身份：非肌层浸润性膀胱癌的膀胱灌注治疗。 FDA 对 TICE BCG 的产品信息中，明确列出其用于膀胱原位癌治疗和预防，以及经尿道切除术后 Ta/T1 乳头状肿瘤复发预防。 BCG膀胱灌注机制图 BCG 的逻辑和 T-VEC 不一样。 它不是把细菌送进全身血液，也不是让细菌在全身“追杀肿瘤”。它是通过导尿管把 BCG 灌注到膀胱里，让它主要在膀胱局部发挥作用。 第一步，膀胱灌注。 医生将 BCG 悬液注入膀胱，让它接触膀胱黏膜和残留肿瘤细胞。这也是为什么 BCG 特别适合膀胱癌这个场景：膀胱是一个相对封闭、可以局部给药的器官。 第二步，局部免疫被唤醒。 BCG 可以附着在膀胱上皮和肿瘤细胞附近，引发局部免疫反应。巨噬细胞、树突状细胞、中性粒细胞、NK 细胞和 T 细胞会被招募过来，细胞因子也会增加。 用普通话讲，就是原本安静的膀胱局部，突然变成一个免疫系统高度警觉的地方。 第三步，清除残留肿瘤细胞，降低复发风险。 非肌层浸润性膀胱癌常常在手术切除后仍有复发风险。BCG 的价值，不是像手术刀一样切掉肿瘤，而是在术后通过局部免疫刺激，帮助清理残留风险，降低复发。 所以，BCG 不是典型意义上“细菌直接溶解肿瘤”的方案。它更像是“用细菌训练和激活局部免疫系统”。 但从治疗思想上看，它是细菌参与抗肿瘤治疗最成熟的现实样板。 四、病毒路线和细菌路线有什么不同？ 这两条路线都在利用微生物，但思路不完全一样。 溶瘤病毒：进入细胞内部的复制型武器。 它的关键问题是：能不能选择性进入并复制？能不能裂解肿瘤？能不能激活后续免疫？能不能避开过强的抗病毒清除？ 细菌路线：利用肿瘤微环境和局部免疫反应。 它的关键问题是：能不能安全地定植或停留在肿瘤区域？能不能激活合适强度的免疫？会不会造成感染风险？工程化改造后能不能稳定可控？ 如果把它们放进肿瘤免疫的大框架里，二者共同目标都是把肿瘤从“免疫系统不愿意进去的地方”，改造成“免疫系统愿意进去、看得见、打得动的地方”。 五、现在市面上真正能看到哪些主流产品？ 讲溶瘤治疗，很容易一不小心讲成“未来概念”。但这条路不是完全停在实验室里，已经有一些产品进入了真实市场。 Imlygic，也就是 T-VEC。 这是目前最具代表性的溶瘤病毒产品之一，由 Amgen 旗下 BioVex 开发，基于 HSV-1 改造。美国 FDA 页面列出的适应证，是用于黑色素瘤患者术后复发、不可切除的皮肤、皮下和淋巴结病灶的局部治疗。 它的意义在于：证明“工程化溶瘤病毒 + 局部注射 + 免疫激活”可以成为获批药物。 Oncorine，也就是 H101。 这是中国批准上市的溶瘤腺病毒产品，由上海三维生物开发，通常被认为是全球最早获批的溶瘤病毒药物之一。 它基于 5 型腺病毒改造，主要用于头颈部肿瘤相关场景，常见讲法是与化疗联合使用。它的临床定位和国际影响力不如 T-VEC 那么大，但在“溶瘤病毒从概念走向产品”这件事上非常重要。 Delytact，也就是 teserpaturev / G47Δ。 这是日本批准的溶瘤 HSV-1 产品，用于恶性胶质瘤相关治疗场景。它同样属于工程化疱疹病毒路线。 和 T-VEC 相比，它面向的是脑肿瘤这样更复杂、更难递送的场景，因此更适合作为“溶瘤病毒进入高难度实体瘤”的案例来理解。 TICE BCG。 这是现实中最成熟、最常被使用的细菌抗肿瘤免疫产品之一。FDA 页面列出的适应证包括膀胱原位癌的治疗和预防，以及 Ta/T1 乳头状肿瘤经尿道切除后的复发预防。 它不是“细菌直接吃掉肿瘤”的药，而是通过膀胱局部灌注，激活局部免疫反应，从而降低复发风险。 六、为什么溶瘤治疗常常要联合用药？ 因为肿瘤不是一团被动等待攻击的细胞。 它有免疫抑制微环境，有异常血管，有物理屏障，有抗原异质性，也有不断进化的逃逸能力。单靠一个病毒或一种细菌，通常很难解决所有问题。 所以现在更被看好的方向，是联合治疗。 比如，溶瘤病毒先在肿瘤局部造成裂解和炎症，释放抗原，把“冷肿瘤”变成“热肿瘤”；然后再联合 PD-1/PD-L1 抑制剂，让被激活的 T 细胞不要被刹车按住。 细菌路线也类似。工程菌可以被设计成携带免疫因子、局部释放药物，或者改变肿瘤微环境，再与免疫检查点抑制剂、放疗、化疗或细胞治疗配合。 未来的重点，可能不是问“溶瘤治疗能不能单药治愈癌症”，而是问：它能不能成为肿瘤免疫治疗里的“点火器”。 七、这条路线最难的地方在哪里？ 第一是安全性。 病毒和细菌都不是普通小分子药物。它们会复制、会诱导免疫反应，也可能引发炎症、感染或不可预期的扩散。因此，减毒设计、复制控制、给药路径和患者筛选非常关键。 第二是递送。 肿瘤并不是一块均匀海绵。药物打进去以后，能不能扩散到足够多的区域？静脉给药时会不会被免疫系统迅速清除？这些都是现实问题。 第三是疗效预测。 哪些患者更适合？哪些肿瘤更容易从“冷”变“热”？哪些生物标志物能提示疗效？如果没有这些答案，临床开发就容易变成盲试。 第四是生产和质控。 活病毒、活细菌或工程菌不是普通化合物。批次一致性、遗传稳定性、污染控制、储存运输、给药操作，都会影响真实落地。 八、怎么理解它的前景？ 溶瘤治疗不是万能钥匙，也不是肿瘤治疗里的边角料。 它最有价值的位置，可能是连接“局部治疗”和“系统免疫”的桥梁。 T-VEC 说明，经过改造的病毒可以被做成真实药物，进入临床应用；BCG 说明，细菌激活局部抗肿瘤免疫这件事，并不是停留在概念里，而是已经在膀胱癌治疗中用了很多年。 但它们也同时提醒我们：微生物疗法的成功高度依赖场景。能不能局部给药？肿瘤是否可接触？免疫系统是否还有反应能力？联合治疗怎么设计？这些都会决定最后效果。 所以，对溶瘤治疗最稳妥的判断是： 它不是用病毒或细菌“神奇吃掉癌症”，而是利用微生物的复制、定位和免疫刺激能力，把肿瘤现场改造成一个更容易被免疫系统识别和攻击的战场。 真正的未来，不一定是单打独斗，而是和免疫检查点抑制剂、细胞治疗、放疗、化疗、肿瘤疫苗和工程化递送系统一起，成为组合疗法中的关键一环。 主要参考来源 [1] FDA：TICE BCG 产品信息，列明 BCG Live 的适应证包括膀胱原位癌治疗/预防，以及 Ta/T1 乳头状肿瘤经尿道切除后的复发预防。https://www.fda.gov/vaccines-blood-biologics/vaccines/tice-bcg [2] FDA：IMLYGIC 产品信息，列明 talimogene laherparepvec 的商品名、生产企业和黑色素瘤局部治疗适应证。https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/imlygic [3] FDA：ADSTILADRIN 产品信息，列明 nadofaragene firadenovec-vncg 为用于 BCG 无应答高危非肌层浸润性膀胱癌的腺病毒载体基因治疗产品。https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/adstiladrin [4] FDA：ANKTIVA 批准信息，列明 nogapendekin alfa inbakicept-pmln 与 BCG 联合用于 BCG 无应答非肌层浸润性膀胱癌。https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer [5] Talimogene laherparepvec / T-VEC 公开药物资料：T-VEC 为 HSV-1 改造的溶瘤病毒，采用瘤内注射，用于部分不可手术黑色素瘤，并通过肿瘤裂解和 GM-CSF 介导的免疫激活发挥作用。https://en.wikipedia.org/wiki/Talimogene_laherparepvec [6] Oncorine / H101 与 Delytact / G47Δ 公开资料：用于梳理中国、日本已上市溶瘤病毒产品的基本定位和历史背景。https://en.wikipedia.org/wiki/Oncolytic_virus [7] OPTiM 研究与 T-VEC 相关综述资料：T-VEC 的临床开发和机制讨论主要围绕瘤内注射、肿瘤细胞裂解、GM-CSF 表达和系统性抗肿瘤免疫反应展开。 免责声明 本文用于科普和产业技术讨论，不构成医疗建议、投资建议或产品推荐。具体诊断、治疗选择和用药方案必须由专业医生根据患者病情、指南和获批适应证决定；文中涉及的药物、企业和研发进展，请以监管机构、企业公告、论文原文和临床试验登记信息为准。

Five issued U.S. patents cover the combination of ImmunityBio’s IL-15 receptor agonist (NAI) with Bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer treatment, with terms extending through at least 2035 Claims cover methods of treating non-muscle invasive bladder cancer (NMIBC) including BCG-naïve disease, defined-dose pharmaceutical compositions matching the approved NAI + BCG intravesical regimen, and two-vial commercial kits Portfolio reinforces ImmunityBio's IL-15 receptor agonist plus BCG position as the Company executes its exclusive U.S. Tokyo-172 BCG supply agreement with Japan BCG Laboratory and continues to develop Recombinant BCG (rBCG) to enhance USA supply CULVER CITY, Calif.--(BUSINESS WIRE)--ImmunityBio, Inc. ( NASDAQ: IBRX ), a vertically integrated commercial-stage immunotherapy company, today announced that five United States patents have been issued to ImmunityBio covering the combination of its IL-15 receptor agonist ANKTIVA ® (nogapendekin alfa inbakicept-pmln) with Bacillus Calmette-Guérin (BCG) for the treatment of cancer. The five patents (U.S. Patent Nos. 11,173,191; 11,679,144; 11,890,323; 12,268,731; and 12,318,432) with terms extending through at least 2035 include compositions of combinations of ANKTIVA and BCG. Together they protect the approved ANKTIVA plus BCG product, the specific intravesical dosing regimen, the two-vial commercial kit, and methods of treating non-muscle invasive bladder cancer (NMIBC) including BCG-naïve disease and bladder cancer. The issued patent portfolio establishes composition-of-matter and method-of-use protection for ImmunityBio’s IL-15 receptor agonist and BCG combination platform through the next decade and beyond. This intellectual property position supports the Company’s commercial ANKTIVA plus BCG franchise in BCG-unresponsive NMIBC and bladder cancer, its pending supplemental BLA for BCG-unresponsive papillary-only disease, and the advancing QUILT-2.005 registrational trial evaluating ANKTIVA plus BCG versus BCG alone in BCG-naïve NMIBC carcinoma in situ . The patent portfolio also intersects with ImmunityBio’s recently announced exclusive U.S. Development and Supply Agreement with Japan BCG Laboratory for the Tokyo strain of BCG (Tokyo-172), which is supported by the positive Phase III SWOG S1602 results demonstrating non-inferiority of Tokyo-172 BCG versus TICE BCG on high-grade recurrence-free survival (HR 0.82; 95.8% CI 0.63–1.08) in 984 randomized patients with BCG-naïve high-grade NMIBC. As ImmunityBio engages with the FDA to pursue U.S. approval of Tokyo-172 BCG, the issued patent estate protects the combination of any approved BCG strain with the Company’s IL-15 receptor agonist platform. “Over the past decade, we have built an integrated immunotherapy platform grounded in the science of IL-15 and its capacity to activate NK cells, CD8+ T cells, and memory T cells without expanding suppressive regulatory T cells. These five issued patents protect that science at every layer that matters commercially: the compositions of matter, the method of treatment, the wild-type and mutant IL-15 plus BCG compositions, the intravesical dosing regimen, and the two-vial kit physicians administer. The IL-15 and BCG combination is the backbone of our bladder cancer franchise, and this patent estate protects it through at least 2035. In a similar vein, ImmunityBio has received issued patents covering the combination of ANKTIVA with checkpoint inhibitors,” said Patrick Soon-Shiong, M.D., Founder, Executive Chairman and Global Chief Medical and Scientific Officer of ImmunityBio. “This patent portfolio provides long-term protection for a cornerstone of ImmunityBio’s commercial franchise at a time when we are expanding the clinical utility of ANKTIVA plus BCG across multiple NMIBC settings, securing a second BCG supply source for the U.S. market, and generating 700% year-over-year revenue growth. The combination of durable patent protection, validated clinical data, and supply chain diversification positions ANKTIVA plus BCG as the standard of care in this disease for years to come,” said Richard Adcock, President and Chief Executive Officer of ImmunityBio. U.S. Patent No. 11,173,191 (issued November 16, 2021) covers the core method of treating cancer by administering BCG together with the IL-15N72D:IL-15RαSu/Fc complex (ALT-803/ANKTIVA), with dependent claims specific to bladder cancer, NMIBC, BCG-naïve NMIBC, and intravesical administration. This is the foundational method-of-treatment claim that reads directly on the FDA-approved use of ANKTIVA plus BCG. U.S. Patent No. 11,679,144 (issued June 20, 2023) covers the pharmaceutical composition combining BCG with a wild-type IL-15:IL-15RαSu complex, including the two-vial kit format (one vial BCG, one vial IL-15:IL-15RαSu, plus directions for use in treating cancer including bladder cancer). This broadens composition and product-form protection beyond the IL-15N72D mutant to wild-type IL-15 combinations. U.S. Patent No. 11,890,323 (issued February 6, 2024) covers the method of treating NMIBC, including BCG-naïve NMIBC, by intravesical instillation of BCG plus a wild-type IL-15:IL-15RαSu complex. This patent pairs with 11,173,191 to cover both the IL-15 mutant and wild-type forms of the combination, closing a potential design-around route. U.S. Patent No. 12,268,731 (issued April 8, 2025) covers the defined-dose composition itself: a single intravesical dose, matching the ANKTIVA plus BCG dosing regimen used in the FDA-approved label and in the QUILT-3.032 and QUILT-2.005 trials. Claims also cover the corresponding two-vial bladder cancer treatment kit. U.S. Patent No. 12,318,432 (issued June 3, 2025) covers the commercial two-vial kit itself: a first vial of BCG and a second vial of ANKTIVA (dimeric IL-15RαSu/Fc plus two IL-15N72D molecules) with instructions for treating neoplasia. This patent protects the as-supplied product configuration that physicians receive and administer. About ANKTIVA ® (nogapendekin alfa inbakicept-pmln) The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA ® overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response. ANKTIVA® is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA ® mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and driving the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. Important Safety Information U.S. IMPORTANT SAFETY INFORMATION INDICATION AND USAGE: ANKTIVA® is an interleukin-15 (IL-15) receptor agonist indicated with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. WARNINGS AND PRECAUTIONS: Risk of Metastatic Bladder Cancer with Delayed Cystectomy. Delaying cystectomy can lead to the development of muscle-invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after a second induction course of ANKTIVA® with BCG, reconsider cystectomy. DOSAGE AND ADMINISTRATION: For Intravesical Use Only. Do not administer by subcutaneous or intravenous routes. Please see the complete Indication and Important Safety Information and Prescribing Information for ANKTIVA® at Anktiva.com. Investigational Use Notice: The Tokyo strain of BCG (manufactured by Japan BCG Laboratory) and recombinant BCG or rBCG (manufactured by Serum Institute of India under ongoing partnership with ImmunityBio) are investigational in the United States and have not been approved by the FDA. The safety and effectiveness of these investigational products have not been established. Availability of rBCG is limited to ImmunityBio's FDA Expanded Access Program for eligible patients. To enroll in the Expanded Access Program for recombinant BCG, please visit About ImmunityBio ImmunityBio, Inc. is a biotechnology company focused on innovating, developing, and commercializing next-generation immunotherapies designed to activate the patient's immune system and deliver durable protection against cancer and infectious diseases. Our approach harnesses both the adaptive and innate immune systems with the goal of restoring immune function and generating lasting immunological memory in patients. At the core of our strategy is the Cancer BioShield™ platform, which is designed to stimulate critical lymphocytes, including natural killer (NK) cells, cytotoxic T cells, and memory T cells via our proprietary IL-15 superagonist. Our Cancer BioShield platform is anchored by this antibody-cytokine fusion protein and is complemented by an investigational portfolio that includes adenovirus-vectored vaccines, allogeneic (off-the-shelf) and autologous NK-cell therapies, and additional immunomodulators intended to promote immunogenic cell death and support durable immune responses while potentially reducing reliance on high-dose chemo-radiation therapy. For more information, visit ImmunityBio.com and connect with us on X (Twitter), Facebook, LinkedIn, and Instagram. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements including, but are not limited to, statements regarding the expected benefits, scope, validity, enforceability, and commercial value of ImmunityBio's patent portfolio; the expected duration of patent protection for ANKTIVA® in combination with BCG through at least 2035; the potential for patent term extensions or adjustments; the commercial and competitive advantages afforded by the issued patents; the Company's ability to maintain and expand its intellectual property position around IL-15 receptor agonist and BCG combinations; expectations regarding the QUILT-2.005 registrational trial and potential supplemental BLA approval for BCG-unresponsive papillary-only disease; anticipated revenue growth and market expansion for the ANKTIVA plus BCG franchise; the successful development and U.S. regulatory approval of Tokyo-172 BCG; and the Company's ability to execute its U.S. supply agreement with Japan BCG Laboratory. These forward-looking statements are based on management's current expectations and are subject to risks and uncertainties, known and unknown, that may cause actual results to differ materially from those projected. Such risks and uncertainties include, but are not limited to: challenges to the validity or enforceability of our patents in litigation or administrative proceedings; potential infringement claims by third parties; the possibility that competitors may design around our patents or develop alternative therapies; uncertainties regarding patent term extension or adjustment calculations; the risk that regulatory authorities may not approve Tokyo-172 BCG or the supplemental BLA for papillary-only disease; changes in patent laws and regulations; the outcome of ongoing and future clinical trials; market acceptance of ANKTIVA plus BCG; manufacturing and supply chain risks; and other factors discussed in ImmunityBio's filings with the U.S. Securities and Exchange Commission (SEC), including the "Risk Factors" sections of the Company's Annual Report on Form 10-K filed on February 23, 2026 and most recent Quarterly Report on Form 10-Q filed on May 7, 2026. ImmunityBio undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Contacts Investors Hemanth Ramaprakash, PhD, MBA ImmunityBio, Inc. +1 858-746-9289 Hemanth.Ramaprakash@ImmunityBio.com Media Sarah Singleton ImmunityBio, Inc. +1 415-290-8045 Sarah.Singleton@ImmunityBio.com