The urgent need to develop a vaccine to prevent SARS-CoV-2 pandemic is now the main focus all over the world. Over the past decade, scientists and drug industries have been works on different kinds of human threatening disease like H1N1 influenza, Ebola, Zika, SARS-CoV, MERS, etc. The knowledge to work in this area, helping the researcher a lot to develop a vaccine in at Pandemic Speed. However, the development of a new drug and starting application on human heal is a time-consuming manner. It becomes very hard in the case of COVID-19 as the virus characters changing rapidly. Here we discuss whether the anti-cancer immunotherapy could give some hope to protect against COVID-19 and also enrollment of cancer vaccine which started a randomized clinical trial to boost the treatment strategies against COVID-19 on an emergency basis.
“Mind the gap” is as an audible or visual warning phrase to subway passengers in London of the significant space between the train door and station platform. We utilized this phrase to caution people to be mindful of the significant gap in knowledge about COVID-19 treatment and Cancer Immunotherapy. From the end 2019, a novel coronavirus causing respiratory-related disease known as COVID-19 has spreading rapidly among the whole world. The number of infected persons increasing rapidly worldwide and still continuing. Since the scientific knowledge gained from research on our body immune system and its reaction against foreign particles, it might be helpful to make prevention of future outbreaks. The immunotherapy and research specially help to understand the mechanism of action of virus and other foreign particle in human body and its prevention. On the other hand, cancer immunotherapy is now rapidly growing because of its mechanism is more target specific than chemotherapy or radiation treatment. Moreover, the immunotherapy has less side effects that chemotherapy and radiation commonly have i.e. damage healthy cells, commonly leading to hair loss. The main concern now a days whether anti-cancer immunotherapy can be used to treat COVID-19 or not? Basically, immunotherapy works on specific cancer immune system not all over the immune system. Sometimes immunotherapy leads to side effects due to its general immune system activation. Currently some immunotherapy used live pathogen to treat cancer [1-2] but these treatments only shown impact on a limited number of patients and cancer types. So, it is important to understand the fundamental differences between cancer immunotherapy and Immunotherapy to treat COVID-19 for the prevention of pandemic. There is an urgent need where Immuno-Oncology can help to make strategies to treat COVID-19. In this review we present a comprehensive analysis of available information on the drugs which used to treat cancer that can also being use for COVID-19 treatment to shortened the time length during the current outbreak.
Viral vaccines that using to treat Cancer
Seasonal influenza virus infection is the most common viral infection by which people suffer every year. The Centers for Disease Control and Prevention (CDC) mention that, the patients admitted hospital with respiratory illness most of them suffer from influenza-like illness .
As per the report, in USA approximately 5%–20% of people infected by influenza virus in each season [4-5]. As per CDC 2019-2020 estimation (www.cdc.gov) 740000 was hospitalized due to flu where near about 64000 died due to this virus . In their article mentioned many other counties estimation on influenza vaccine. To prevent the seasonal flu there is a huge demand in FDA-approved seasonal flu shots. Research is now focus to understand how immune responses against pathogens like influenza and their components could improve our much weaker immune response against some tumor. However, there are many factors involve in live infections, which done not found in tumors. It was found that, direct injection of flu vaccine into the skin melanoma caused the tumors grow slower  by increasing immune-stimulating dendritic cells in the tumor, resulting an increase in CD8+ T-cells, which recognize and kill cancer cells. Human dendritic cells (DCs) play a crucial role in the immunity during vaccination against influenza. It was well known that Influenza vaccines trigger immunity through induce an IFN response in DCs, which help to increase the vaccine efficiency .There is evidence of clinical trial  which proves dendritic cells vaccine (DCV) has minimal toxicity in patients with metastatic melanoma and its gives long time survival benefit. In this regard there is a major question arise that, can a Flu Shot be use full to treat Cancer? According to a publication in Proceedings of the National Academy of Sciences (PNAS), the patients receiving seasonal influenza vaccination may experience multiple clinical benefits like cancer immunotherapy. In a mouse model study, virus-specific memory T cells shows an alarming effect to reduce the tumor growth not only in lung tumour but also in metastatic triple-negative breast cancer . Recently a study published where it was shows that flu vaccine is safe and dose not exacerbates immune events in cancer patients treated with immune checkpoint inhibitors (ICIs). However another study that contain 162 patients, showing no impact in response to flu vaccines in patients receiving checkpoint inhibitors . Since the flu shots has been used by millions of people and have already proved its safe, so research start to use flu shots to treat cancer but to start application largely its need more clinical trial outcome. Since, combination therapies are current frontline therapies for cancer, researcher start to use Influenza vaccines combined with cancer immunotherapy.
There are several targets of vaccine that is under evaluation in clinical trials which are-CEA, Cytomegalovirus (CMV)-related antigens: foreign viral proteins expressed by CMV-infected cancer cells; Folate-related proteins; EGFR; HER2;Human Papilloma Virus (HPV)-related antigens; MAGE antigens; Mesothelin; MUC-1;NY-ESO-1;P53; PAP and PSA, Personalized neoantigens; Ras; Survivin; WT1. Most significant FDA-approved vaccines that are used for cancer immunotherapy are listed in Table 1 .
|Vaccine name||Cancer Treatment|
|Gardasil®||HPV-related anal, cervical, head and neck, penile, vulvar, and vaginal cancers|
|Hepatitis B (HBV) vaccine (HEPLISAV-B®)||can help prevent the development of HBV-related liver cancer|
|Bacillus Calmette-Guérin (BCG)||early-stage bladder cancer|
|Sipuleucel-T (Provenge®)||approved for prostate cancer|
In their article describe in detail about therapeutic cancer vaccine and its future platform. Future directions are needed to involve the viral-based vaccines to treat patients regards adjuvant and neo-adjuvant settings and in combination with immunotherapy. An appropriate clinical endpoint is needed for therapeutic vaccines which will define the main strategies for the combination immunotherapy for cancer treatment.
Cancer vaccine to Treat Covid-19
Since SARS-CoV-2 coronavirus that causes the respiratory-related disease known as COVID-19 has spread widowed manner, researchers are working on preventive vaccines in an urgent basis. Based on the results of annual flu vaccines immunotherapy, researchers believe that these medicines may lead the immune system to act aggressively against COVID-19. According to a retrospective study from New York city cancer patients receiving immunotherapy were at increased risk for severe outcomes from COVID-19 . But on the other hand study find that cancer immunotherapy does not increase risk for melanoma patients . Now researchers discovered that cancer immunotherapy tolls can be use for COVID-19 treatment. They identified the right protein sequence target which used for cancer therapy also use for COVID-19 prevention . Many research and clinical trial is going on optimizing designed vaccine which can maximizing the immune response and disease exacerbation. The main target is to produce vaccine that are safe and effective. Some of the important Cancer immune therapy drug that is under Clinical trials worldwide, are mentioned in Table 2.
|Drug Name||Mode of Action||Used for Cancer Therapy||Progress in COVIDtrial||Reference||Country|
|Infliximab||TNFα inhibitors currently FDA-approved for the treatment of autoimmune disorders, including Crohn's disease and rheumatoid arthritis||Terminated: Breast Cancer||Phase II||NCT04425538||Tufts Medical Center Boston, Massachusetts, United States|
|FT516||It is an off-the-shelf cryopreserved NK cell product derived from an iPSC that was transduced with a high affinity, ADAM17 non-cleavable CD16 (Fc receptor) that maintains CD16 on the cell surface, which remains fully functional after NK cell activation.||As monotherapy in acute myeloid leukemia (AML) and in combination with CD20 directed monoclonal antibodies in B-cell lymphoma.||Phase I||NCT04363346||University of Minnesota Minneapolis, Minnesota, United States|
|Pamrevlumab||Pamrevlumab is a first-in-class antibody that inhibits the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders, characterized by persistent and excessive fibrous tissue which can lead to organ dysfunction and failure, and in cancer, characterized by promotion of tumor growth.||In Phase III clinical trial of Pamrevlumab in Combination With Gemcitabine Plus Nab-paclitaxel (G/NP) as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer||Phase II||NCT04432298||Research Center Greensboro, North Carolina, United States|
|Losartan||Losartan is an angiotensin II receptor blocker (ARB). It keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.||1. Phase I trial in Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer.2. Phase I trial with Sunitinib in Treatment of Osteosarcoma||Phase I||NCT04335123||University of Kansas Medical Center Kansas City, Kansas, United States|
|Tofacitinib||Tofacitinib is a JAK inhibitor. These drugs work by interfering with the inflammatory processes within the immune system that cause the symptoms of rheumatoid arthritis.||Phase I trial with LMB-100 in Neoplasms With Mesothelin Expression, Epithelioid Mesothelioma, Extrahepatic Cholangiocarcinoma, Pancreatic Adenocarcinoma||Phase II||NCT04412252||University Hospitals ClevelandMedical Center Cleveland,Ohio, United States|
|Famotidine||Famotidine is a histamine-2 receptor antagonist, widely available.||1. Phase I trial with XL281 is complete in solid tumors like Non-small-cell Lung Cancer,Colorectal Cancer Papillary Thyroid Cancer, Melanoma.2. Phase I trial with Savolitinib is complete in solid tumors.||Use in Non-hospitalized Patients With COVID-19||NCT04389567||Cold Spring HarborLaboratory Cold Spring Harbor, New York,United States|
|Leflunomide||Leflunomide, is an inhibitor of dihydroorotate dehydrogenase (DHODH).It belongs to a class of drugs calleddisease-modifying antirheumatic drugs (DMARDs).||1. Phase I/II Trial in Women With Previously Treated Metastatic Triple Negative Cancers.2. Phase II/III Study with Mitoxantrone/ Prednisone in Patients With Hormone-Refractory Prostate Cancer.3. Phase II study for Patients With Anaplastic Astrocytoma4. Phase III Randomized versus Procarbazine for Patients With Glioblastoma Multiforme.||Phase I||NCT04361214||University of Chicago Chicago, Illinois, United States|
|Hydroxychloroquine||Hydroxychloroquine is an Autophagy inhibitor, when given in combination with cytotoxic agents have been found to suppress tumour growth and trigger cell death to a greater extent than chemotherapy alone, both in vitro and in vivo.||1. Phase II in Previously Treated Patients With Metastatic Pancreatic Cancer.2. Phase I/II Study of Hydroxychloroquine and Itraconazole as Therapy for Prostate Cancer.3. Phase II study with Sorafenib in Hepatocellular Cancer||Phase IV||NCT04382625||Kootenai Health Coeur d'Alene, Idaho, United States|
|Enoxaparin||Enoxaparin is an anticoagulant (blood thinner) used to prevent blood clots that are sometimes called deep vein thrombosis (DVT), which can lead to blood clots in the lungs.||1. Phase II study of Rosuvastatin and Enoxaparin in Ovarian Cancer.2. Phase II/III Trial Of Simultaneous Pancreatic Cancer Treatment With Enoxaparin and ChemoTherapy.3. Phase III Study of Standard Treatment with Enoxaparin in Small Cell Lung Cancer.4. Phase II Trial of Enoxaparin Thromboprophylaxis in Cancer Patients With Elevated Tissue Factor Bearing Microparticles.5. Phase III-b, Multi-centre,Open-label, Parallel Study of Enoxaparin With Chemotherapy in Patients with Gastric andGastro-oesophageal Cancer.||Phase III||NCT04359277||NYU Langone HealthNew York, New York, United States|
|Tocilizumab||Tocilizumab is a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor.||1. Phase I Trial of Trastuzumab and Pertuzumab in Combination With Tocilizumab in Metastatic HER2 Positive Breast Cancer.2. Phase I/II trial of Combination of Chemotherapy With Tocilizumab and Peg-Intron in Patients With Recurrent Ovarian Cancer.3. Phase II trial of Ipilimumab, Nivolumab, Tocilizumab and Radiation in Pretreated Patients With Advanced Pancreatic Cancer.4. Phase II study of Atezolizumab With Tocilizumab in Prostate Cancer.5. Phase II study of Nab-Paclitaxel and Gemcitabine With or Without Tocilizumab in Pancreatic Cancer.6. Phase II study of Tocilizumab in Hospitalized Cancer Patients With SARS-CoV-2.||Phase III||NCT04412772||Queen's Medical Center Honolulu, Hawaii,United States|
|Ulinastatin||Ulinastatin (or urinary trypsinogen inhibitor) is a serine protease inhibitor derived from human urine, with potential protective, anti-fibrinolytic and anticoagulant activities.||1. A Prospective Randomized Trial Comparing Ulinastatin's Protection in Hepatocellular Carcinoma(HCC) Patients'Postoperative Hepatic Failure.2. Phase III trial of Ulinastatin for Reducing Radiation-Induced Oral Mucositis in Nasopharyngeal Carcinoma Patients||Phase I||NCT04393311||Stanford University Stanford, California, United States|
|Imatinib||Imatinib is a tyrosine kinase inhibitor that has been approved for treatment of many hematologic and solid neoplasm.||1. Phase II Trial of Docetaxel Plus Imatinib Mesylate in Metastatic Breast Cancer2. Phase II Trial Of Imatinib Mesylate In Combination With Capecitabine In Metastatic Breast Cancer3. Phase II Trial Imatinib Mesylate in Combination With Docetaxel for the Treatment of Ovarian Cancer and Primary Peritoneal Carcinomatosis4. Phase I Study of Capecitabine, Cisplatin and Imatinib in Metastatic Gastric Cancer.5. Phase II Trial of Imatinib Mesylate Maintenance Therapy in Patients With Small Cell Lung Cancer.6. Phase I/II Study of Imatinib Mesylate and Gemcitabine for Advanced Pancreas Cancer||Phase III||NCT04394416||University of Maryland Medical CenterBaltimore, Maryland, United States|
|N-acetylcysteine||NAC is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. It is a thiol-antioxidant.||1. Phase I Study of Anti-oxidant Supplementation With N-Acetyl Cysteine in Breast Cancer2. Phase II study in Head and Neck Cancer patients undergoing Radiation Therapy||Phase II||NCT04374461||Memorial Sloan Kettering Cancer CenterNew York, New York, United States|
|Atovaquone||Atovaquone is an anti-protozoal drug that significantly reduces oxygen consumption in a variety of tumour cell lines||1. Early Phase I Study in Non-small Cell Lung Carcinoma2. Early Phase I Study of Atovaquone With Conventional Chemotherapy for Acute Myeloid Leukemia (AML)||Phase II||NCT04339426||Honor Health Scottsdale, Arizona, United States|
|Telmisartan||It is an Angiotensin Receptor Blocker.||RetrospectiveStudy of Angiotensin Receptor Blockers in neoplasm. Completed .||Phase II||NCT04360551||University of Hawaii - Manoa, John A Burns School of Medicine UH Clinics at Kakaako Honolulu, Hawaii, United States|
|Tranexamic||TXA is a synthetic analog of lysine amino acid which reversibly binds four to five lysine receptor sites on plasminogen.||Phase III sudy in bone cancer 2 Phase IV study in Surgery of Advanced Ovarian Cancer3. Phase III study of Tranexamic Acid in Preventing Bleeding in Patients With Haematological Malignancies.4. Phase IV stud in Colorectal Cancer Surgery5. Phase III study in Head and Neck Neoplasms||Phase II||NCT04338074||University of Alabama at Birmingham Birmingham, Alabama, United States|
|Bicalutamide||It is an oral, non-steroidal, androgen receptor (AR) antagonist.||1. A Phase II study in Metastatic Breast Cancer.2. Phase II RAD001 and Bicalutamide for Androgen Independent Prostate Cancer3. Phase II Enzalutamide Versus Bicalutamide in Prostate Cancer4. Phase III Study ofBicalutamide Versus Chemotherapy in AR Positive Metastatic Triple Negative Breast Cancer5. Phase II Exemestane With or Without Bicalutamide in Stage IV Prostate Cancer||Phase II||NCT04374279||Johns Hopkins Hospital Baltimore, Maryland, United States|
|Sirolimus||Known as rapamycin, inhibitor of mTORpathway||1. Phase II Study of Rapamycin and Trastuzumab in Patients With HER-2 Receptor Positive Metastatic Breast Cancer2. Phase II in Treating Patients With Advanced Pancreatic Cancer3. Phase II Trial, Efficacy of Temsirolimus for Patients With Advanced Bladder Cancer||Phase II||Loyola University Medical Center Chicago, Illinois, United States University of Cincinnati Cincinnati,Ohio, United States|
|Colchicine||Anti-inflammatory in nature and It can treat and prevent gout attacks.||Phase II Evaluation the Palliative Effects of Colchicine on Primary Hepatic Malignant Tumors Unable to Receive Curative Treatment||Phase II||NCT04355143|
Now a day’s Chimeric antigen receptor (CAR) T-cell therapy is very promising immune therapy which use in cancer treatment . Cytokine release syndrome (CRS) is an overwhelming and potentially life-threatening inflammatory response often seen in cancer patients. The CRS like symptoms also found in COVID-19 patients . Tocilizumab is the drug of choice to treat CRS, where the customized monoclonal antibody targeting the IL-6 receptor. This drug is under Phase III trial I to treat COVID-19. Another drug. CD24Fc also started to use as immunomodulator to treat COVID-19 show/NCT04317040]. Cell based therapeutic vaccine like aAPC Vaccine [https://clinicaltrials.gov/ct2/show/ NCT04299724] where the artificial dendritic cells is to be use to activate and stimulate T cell proliferation. Lopinavir-Ritonavir a well-known and established drug used for different cancer treatment [18-19]. As a very well-known antiviral drug, Lopinavir-Ritonavir was widely used for laboratory research to treat SARS-Cov-2 prevention. According to a study based on 199 patients, this drug dose not contain any significant effect to clinical improvement and reduce mortality in COVID-19 patients. On 4th July, 2020 WHO circulated a recommendation to discontinue the use of Lopinavir-Ritonavir after analysis the Solidarity trial interim results . Considering all of this we need to wait until the completion of clinical trial to get new class of emerging therapy is aimed to prevent COVID-19.
In conclusions, COVID-19 pandemic giver very short time to find a proper therapeutic challenge. However, in global emergency, investigations progress rapidly and now phase III trials of new medications already started. As the whole process to approve a new drug which safe and effective, is time consuming. So, several drugs have been re-considered to treat COVID-19 which have been used in cancer therapy. This review considered the cancer immunotherapeutic agents that are potentially suitable drugs consider to treat COVID-19 to accelerate the process. This pandemic generated a endless demand for vaccine all over the world. We should continuing the clinical trial and developing most promising vaccine which can help us not only protect from the current pandemic also help us to gather much knowledge and fill our gaps to protect from future outbreak.
- Sedighi Mansour, Zahedi Bialvaei Abed, Hamblin Michael R., Ohadi Elnaz, Asadi Arezoo, Halajzadeh Masoumeh, Lohrasbi Vahid, Mohammadzadeh Nima, Amiriani Taghi, Krutova Marcela, Amini Abolfazl, Kouhsari Ebrahim. Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Medicine. 2019. DOI
- Vandeven N., Nghiem P.. Pathogen-Driven Cancers and Emerging Immune Therapeutic Strategies. Cancer Immunology Research. 2014; 2(1)DOI
- Centers for Disease Control and Prevention (CDC) 11 April 2017. Overview of influenza surveillance in the United States. Available at: https://www.cdc.gov/flu/weekly/overview.htm. Accessed.
- WebMD. (20 April 2017 ).What are your odds of getting the flu? Available at: http://www.webmd.com/cold-and-flu/flu-statistics.
- National Foundation for Infectious Diseases. (7 July 2017). Understanding influenza. Available at: http://www.nfid.org/newsroom/news-conferences/2015-news-conferences/2015-news-conference/understanding-influenza.pdf.
- Jayasundara Kavisha, Soobiah Charlene, Thommes Edward, Tricco Andrea C, Chit Ayman. Natural attack rate of influenza in unvaccinated children and adults: a meta-regression analysis. BMC Infectious Diseases. 2014; 14(1)DOI
- Palucka A. Karolina, Dhodapkar Madhav V., Paczesny Sophie, Burkeholder Susan, Wittkowski Knut M., Steinman Ralph M., Fay Joseph, Banchereau Jacques. Single Injection of CD34+ Progenitor-Derived Dendritic Cell Vaccine Can Lead to Induction of T-Cell Immunity in Patients With Stage IV Melanoma. Journal of Immunotherapy. 2003; 26(5)DOI
- Athale Shruti, Banchereau Romain, Thompson-Snipes LuAnn, Wang Yuanyuan, Palucka Karolina, Pascual Virginia, Banchereau Jacques. Influenza vaccines differentially regulate the interferon response in human dendritic cell subsets. Science Translational Medicine. 2017; 9(382)DOI
- Dillman Robert O., Cornforth Andrew N., Nistor Gabriel I., McClay Edward F., Amatruda Thomas T., Depriest Carol. Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses. Journal for ImmunoTherapy of Cancer. 2018; 6(1)DOI
- Newman Jenna H., Chesson C. Brent, Herzog Nora L., Bommareddy Praveen K., Aspromonte Salvatore M., Pepe Russell, Estupinian Ricardo, Aboelatta Mones M., Buddhadev Stuti, Tarabichi Saeed, Lee Michael, Li Shengguo, Medina Daniel J., Giurini Eileena F., Gupta Kajal H., Guevara-Aleman Gabriel, Rossi Marco, Nowicki Christina, Abed Abdulkareem, Goldufsky Josef W., Broucek Joseph R., Redondo Raquel E., Rotter David, Jhawar Sachin R., Wang Shang-Jui, Kohlhapp Frederick J., Kaufman Howard L., Thomas Paul G., Gupta Vineet, Kuzel Timothy M., Reiser Jochen, Paras Joyce, Kane Michael P., Singer Eric A., Malhotra Jyoti, Denzin Lisa K., Sant’Angelo Derek B., Rabson Arnold B., Lee Leonard Y., Lasfar Ahmed, Langenfeld John, Schenkel Jason M., Fidler Mary Jo, Ruiz Emily S., Marzo Amanda L., Rudra Jai S., Silk Ann W., Zloza Andrew. Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer. Proceedings of the National Academy of Sciences. 2019; 117(2)DOI
- Failing Jarrett J., Ho Thanh P., Yadav Siddhartha, Majithia Neil, Riaz Irbaz Bin, Shin John Y., Schenk Erin L., Xie Hao. Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab. JCO Oncology Practice. 2020; 16(7)DOI
- Guo C, Manjili MH, Subjeck JR, et al. Therapeutic cancer vaccines: past, present, and future.. Adv Cancer Res. 2013; 119:421-475. DOI
- Robilotti Elizabeth V., Babady N. Esther, Mead Peter A., Rolling Thierry, Perez-Johnston Rocio, Bernardes Marilia, Bogler Yael, Caldararo Mario, Figueroa Cesar J., Glickman Michael S., Joanow Alexa, Kaltsas Anna, Lee Yeon Joo, Lucca Anabella, Mariano Amanda, Morjaria Sejal, Nawar Tamara, Papanicolaou Genovefa A., Predmore Jacqueline, Redelman-Sidi Gil, Schmidt Elizabeth, Seo Susan K., Sepkowitz Kent, Shah Monika K., Wolchok Jedd D., Hohl Tobias M., Taur Ying, Kamboj Mini. Determinants of COVID-19 disease severity in patients with cancer. Nature Medicine. 2020. DOI
- Gonzalez-Cao, Maria, et al. "Cancer immunotherapy does not increase the risk of death by COVID-19 in melanoma patients.". medRxiv. 2020. DOI
- Yarmarkovich Mark, Warrington John M., Farrel Alvin, Maris John M.. Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-Term Population-Scale Immunity. Cell Reports Medicine. 2020; 1(3)DOI
- Wang Zhenguang, Wu Zhiqiang, Liu Yang, Han Weidong. New development in CAR-T cell therapy. Journal of Hematology & Oncology. 2017; 10(1)DOI
- Mehta Puja, McAuley Daniel F, Brown Michael, Sanchez Emilie, Tattersall Rachel S, Manson Jessica J. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020; 395(10229)DOI
- Sato Akinori, Asano Takako, Okubo Kazuki, Isono Makoto, Asano Tomohiko. Nelfinavir and Ritonavir Kill Bladder Cancer Cells Synergistically by Inducing Endoplasmic Reticulum Stress. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 2018; 26(2)DOI
- OKUBO KAZUKI, ISONO MAKOTO, ASANO TAKAKO, SATO AKINORI. Panobinostat and Nelfinavir Inhibit Renal Cancer Growth by Inducing Endoplasmic Reticulum Stress. Anticancer Research. 2018; 38(10)DOI
- World health Organization (WHO)- 4th July, 2020. https://www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19.