Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Arch Razi Inst. 2021 Mar;76(1):1-6. doi: 10.22092/ari.2021.353761.1612. Epub 2021 Mar 1.
The Covid-19 pandemic has brought about rapid change in medical science. The production of new generation vaccines for this disease has surprised even their most optimistic supporters. Not only have these vaccines proven to be effective, but the importance of this disease and pandemic situation also significantly shortened the long-standing process of validating such products. Vaccination is a type of immunotherapy. Researchers have long been looking at vaccines as a possible treatment for cancer (Geynisman et al., 2014). In the same way that vaccines work against infectious diseases, attempts are being made to develop vaccines to identify specific proteins on cancer cells. This helps the immune system recognize and attack cancer cells. Cancer vaccines may help: I) Prevent the growth of cancer cells (Bialkowski et al., 2016), II) Prevent recurrence of cancer (Stanton and Disis, 2015), III) Destroy cancer cells left over from other treatments. The following types of cancer vaccines are being studied: Antigen Vaccines. These vaccines are made from specific proteins or antigens of cancerous cells. Their purpose is to stimulate the immune system to attack cancer cells (Tagliamonte et al., 2014). Whole-Cell Vaccines. A whole-cell vaccine uses the entire cancer cell, not just a specific molecule (antigen), to generate the vaccine. (Keenan and Jaffee, 2012).Dendritic Cell Vaccines. Dendritic cells help the immune system identify abnormal cells, such as cancerous cells. Dendritic cells are grown with cancer cells in the laboratory to produce the vaccine. The vaccine then stimulates the immune system to attack cancer. (Wang et al., 2014; Mastelic-Gavillet et al., 2019). DNA Vaccines. These vaccines are made from DNA fragments of cancer cells. They can be injected into the body to facilitate immune system cells can better respond and kill cancer cells (Gatti-Mays et al., 2017).Other Types of Cancer Vaccines. such as Anti idiotype vaccines. This vaccine stimulates the body to generate antibodies against cancerous cells. An example of an anti-idiotype antibody is Racotumomab or Vaxira (Cancer, 2016). However, conditions and considerations after Corona does not seem to be the same as before. The current pandemic situation has also led to major changes in the pharmaceutical and Vaccine production process and international protocols. Some of the most critical issues that can accelerate the introduction of cancer vaccines are: 1. Typical drug and vaccine development timeline. A typical vaccine needs 5 to 10 years and sometimes longer to design secure funding, and get approval (Figure 1). Less than 10 percent of new drugs, which are entered in the different phases of clinical trials, are advanced to approval by the Food and Drug Administration (FDA)(Cancer, 2020a). However, now the situation is not normal. Dozens of Covid 19 vaccines are starting clinical trials. Some of them use RNA and DNA technology, which delivers the body with missions to produce its antibodies against the virus. There are already at least 254 therapies and 95 vaccines related to Covid-19 being explored. However, it seems that the experiences gained in this pandemic, and advances in technology, may be effective in shortening the production path of other vaccines and drugs and the process of its approval at the national and international levels in the future. In Figure 2, the time course of production of conventional vaccines in comparison with Covid 19 vaccines (Cancer, 2020b) is shown.2. The introduction of messenger RNA (mRNA) technology into the field of prevention and treatment. Over the past decades, this technology has been considered an excellent alternative to conventional vaccination methods. Proper potency and low side effects, the possibility of fast production and relatively low production cost are its advantages. However, until recently, the instability of this molecule has been a major problem in its application. This research was started many years ago by two companies that played a significant role in developing the first Covid vaccines, so BioNTech and Moderna were able to quickly transfer their experience in the field of Covid vaccine development (Pardi et al., 2018; Moderna, 2020). Figure 3 shows how mRNA vaccines work. Bout Pfizer – BioNTech and Moderna mRNA vaccines were more than 90 % effective in preclinical stages. Millions of doses of these two vaccines are currently being injected into eligible individuals worldwide. 3. Considering the use of artificial intelligence in assessing the effectiveness of vaccines. There are always doubts about the effectiveness of the new drug in treating the disease. Once the vaccine is widely available, we will know more about its effectiveness versus it works under carefully controlled scientific testing conditions. Vaccines will continue to be monitored after use. The data collected helps professionals understand how they work in different groups of people (depending on factors such as age, ethnicity, and people with different health conditions) and also the length of protection provided by the vaccine. Artificial intelligence (AI) is an emerging field, which reaches everywhere and not only as a beneficial industrial tool but also as a practical tool in medical science and plays a crucial role in developing the computation vision, risk assessment, diagnostic, prognostic, etc. models in the field of medicine (Amisha et al., 2019). According to the wide range of AI applications in the analysis of different types of data, it can be used in vaccine production, safety assessments, clinical and preclinical studies and Covid 19 vaccines adverse reactions (CDC, 2019). Indeed, most cancer vaccines are therapeutic, rather than prophylactic, and seek to stimulate cell-mediated responses, such as those from CTLs, capable of clearing or reducing tumor burden. There are currently FDA-approved products for helping cancer treatment such as BREYANZI, TECARTUS and YESCARTA for lymphoma, IMLYGIC for melanoma, KYMRIAH for acute lymphoblastic leukemia, and PROVENGE for prostate cancer. Over the past decade, most of BioNTech's activities have been in the field of cancer vaccine design and production for melanoma (two clinical trials), breast cancer (one clinical trial), and the rest concerning viral and veterinary vaccines (two clinical trials). Also Maderno company has been working on Individualized cancer vaccines (one clinical trials), and vaccines for viral infections such as Zika and Influenza and veterinary vaccines (several clinical trials) (Pardi et al., 2018). Therefore, it can be said, mRNA technology that has been the subject of much research into the treatment of cancer has been shifted and rapidly used to produce and use the Covid 19 vaccine. The current pandemic situation has necessitated the acceleration of Covid 19 vaccines and drugs and national and international protocols for their approval. If the currently produced vaccines can continue to be as successful as the preclinical and early phase studies, these changes and evolution have raised hopes for accelerating the use of these technologies and mechanisms in the field of cancer and other diseases vaccines, including HIV and influenza.
Covid-19 大流行给医学带来了快速变化。新一代针对这种疾病的疫苗的问世，甚至令其最乐观的支持者都感到惊讶。这些疫苗不仅被证明是有效的，而且这种疾病和大流行情况的重要性也大大缩短了验证此类产品的长期过程。
疫苗接种是一种免疫疗法。研究人员长期以来一直将疫苗视为治疗癌症的一种可能方法（Geynisman 等人，2014 年）。正如疫苗对抗传染病的作用一样，人们正在尝试开发疫苗来识别癌细胞上的特定蛋白质。这有助于免疫系统识别和攻击癌细胞。癌症疫苗可能有助于：I）阻止癌细胞的生长（Bialkowski 等人，2016 年），II）防止癌症复发（Stanton 和 Disis，2015 年），III）消灭其他治疗方法留下的癌细胞。目前正在研究以下类型的癌症疫苗：
抗原疫苗。这些疫苗是由癌细胞的特定蛋白质或抗原制成的。它们的目的是刺激免疫系统攻击癌细胞（Tagliamonte 等人，2014 年）。
全细胞疫苗。全细胞疫苗使用整个癌细胞，而不仅仅是特定分子（抗原）来生成疫苗。（Keenan 和 Jaffee，2012 年）。
树突状细胞疫苗。树突状细胞有助于免疫系统识别异常细胞，如癌细胞。在实验室中用癌细胞培养树突状细胞以产生疫苗。然后，疫苗刺激免疫系统攻击癌症。（Wang 等人，2014 年；Mastelic-Gavillet 等人，2019 年）。
DNA 疫苗。这些疫苗是由癌细胞的 DNA 片段制成的。它们可以被注射到体内，以促进免疫细胞更好地响应并杀死癌细胞（Gatti-Mays 等人，2017 年）。
其他类型的癌症疫苗，如抗独特型疫苗。这种疫苗刺激身体产生针对癌细胞的抗体。抗独特型抗体的一个例子是 Racotumomab 或 Vaxira（癌症，2016 年）。
然而，大流行后的情况似乎与之前不同。当前的大流行情况也导致了制药和疫苗生产过程以及国际协议的重大变化。可以加速癌症疫苗引入的一些最关键问题是：
典型药物和疫苗的开发时间表。一种典型的疫苗需要 5 到 10 年，有时甚至更长时间才能设计出安全的资金并获得批准（图 1）。在进入临床试验的不同阶段的新药中，不到 10%的药物可以获得食品和药物管理局（FDA）的批准（癌症，2020a）。然而，现在情况并非如此。数十种新冠病毒疫苗正在进行临床试验。其中一些使用 RNA 和 DNA 技术，为身体提供产生针对病毒的抗体的任务。目前已有至少 254 种治疗方法和 95 种与新冠病毒相关的疫苗正在探索中。然而，在这场大流行中获得的经验以及技术的进步，可能会在未来在国家和国际层面有效缩短其他疫苗和药物的生产路径及其批准过程。在图 2 中，比较了常规疫苗（癌症，2020b）的生产时间过程与新冠病毒疫苗的生产时间过程。
将信使 RNA（mRNA）技术引入预防和治疗领域。在过去的几十年中，该技术已被认为是传统疫苗接种方法的绝佳替代方法。适当的效力和低副作用、快速生产的可能性和相对较低的生产成本是其优势。然而，直到最近，该分子的不稳定性一直是其应用的主要问题。这项研究是由两家在开发新冠疫苗方面发挥重要作用的公司开始的，因此 BioNTech 和 Moderna 能够迅速将其在新冠疫苗开发领域的经验转移（Pardi 等人，2018 年；Moderna，2020 年）。图 3 显示了 mRNA 疫苗的工作原理。辉瑞-BioNTech 和 Moderna 的 mRNA 疫苗在临床前阶段的有效性超过 90%。目前，这两种疫苗正在全球范围内为数百万符合条件的个人接种。
考虑在评估疫苗有效性时使用人工智能。对于新药治疗疾病的有效性，总是存在疑问。一旦疫苗广泛可用，我们将更多地了解其在严格控制的科学测试条件下的有效性。疫苗使用后将继续进行监测。收集的数据有助于专业人员了解它们在不同人群（取决于年龄、种族和患有不同健康状况的人等因素）中的作用以及提供的保护期限。人工智能（AI）是一个新兴领域，无处不在，不仅是有益的工业工具，而且在医学领域也是实用工具，在开发计算视觉、风险评估、诊断、预后等模型方面发挥着至关重要的作用。（Amisha 等人，2019 年）。根据人工智能在分析各种类型数据中的广泛应用，可以将其用于疫苗生产、安全性评估、临床前和临床研究以及新冠病毒疫苗不良反应（CDC，2019 年）。
事实上，大多数癌症疫苗都是治疗性的，而不是预防性的，旨在刺激细胞介导的反应，例如来自 CTLs 的反应，这些反应能够清除或减轻肿瘤负担。目前，有 FDA 批准的产品可用于帮助治疗癌症，例如用于淋巴瘤的 BREYANZI、TECARTUS 和 YESCARTA，用于黑色素瘤的 IMLYGIC，用于急性淋巴细胞白血病的 KYMRIAH 和用于前列腺癌的 PROVENGE。在过去的十年中，BioNTech 的大部分活动都集中在黑色素瘤（两项临床试验）、乳腺癌（一项临床试验）和其余病毒和兽医疫苗（两项临床试验）的癌症疫苗设计和生产上。Maderno 公司还一直在研究个体化癌症疫苗（一项临床试验）以及用于寨卡病毒和流感等病毒感染的疫苗和兽医疫苗（几项临床试验）（Pardi 等人，2018 年）。因此，可以说，一直是癌症治疗研究主题的 mRNA 技术已被转移并迅速用于生产和使用新冠病毒疫苗。当前的大流行情况需要加速新冠病毒疫苗和药物的研发以及其在国家和国际层面的批准。如果目前生产的疫苗能够继续像临床前和早期阶段研究那样成功，这些变化和发展为加速这些技术和机制在癌症和其他疾病疫苗（包括 HIV 和流感）领域的应用带来了希望。
