Casting a wider protective net: Anti-infective vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation

McMasters, Malgorzata; Blair, Barbra M.; Lazarus, Hillard M.; Alonso, Carolyn D.

doi:10.1016/j.blre.2020.100779

Cited by 4 publications

(5 citation statements)

References 183 publications

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“…The speed of the COVID 19 vaccine development was [8]. Despite some critical notes [9,10], a few anti-COVID-19 vaccines were approved, and public vaccination procedure have been started. At the same time, various pharmaceuticals compounds against coronavirus infection are still being tested and yet to demonstrate their significantly high efficacy rates over placebo as well as lower mortality.…”

Section: Introductionmentioning

confidence: 99%

Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Chakravarty¹,

Antontsev²,

Khotimchenko³

et al. 2021

Molecules

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The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.

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Section: Introductionmentioning

confidence: 99%

Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Chakravarty¹,

Antontsev²,

Khotimchenko³

et al. 2021

Molecules

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“…Other studies are evaluating different routes of administration such as intra-and peri-lesional injections for skin cancers. Many clinical trials evaluating the potential of sargramostim as an adjuvant for anti-cancer vaccines in diverse settings and improving efficacy of anti-bacterial and -virus vaccines are discussed above (146,147).…”

Section: Discussion and Future Considerationsmentioning

confidence: 99%

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time?

Lazarus

Ragsdale²,

Gale

et al. 2021

Front. Immunol.

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BackgroundSargramostim [recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF)] was approved by US FDA in 1991 to accelerate bone marrow recovery in diverse settings of bone marrow failure and is designated on the list of FDA Essential Medicines, Medical Countermeasures, and Critical Inputs. Other important biological activities including accelerating tissue repair and modulating host immunity to infection and cancer via the innate and adaptive immune systems are reported in pre-clinical models but incompletely studied in humans.ObjectiveAssess safety and efficacy of sargramostim in cancer and other diverse experimental and clinical settings.Methods and ResultsWe systematically reviewed PubMed, Cochrane and TRIP databases for clinical data on sargramostim in cancer. In a variety of settings, sargramostim after exposure to bone marrow-suppressing agents accelerated hematologic recovery resulting in fewer infections, less therapy-related toxicity and sometimes improved survival. As an immune modulator, sargramostim also enhanced anti-cancer responses in solid cancers when combined with conventional therapies, for example with immune checkpoint inhibitors and monoclonal antibodies.ConclusionsSargramostim accelerates hematologic recovery in diverse clinical settings and enhances anti-cancer responses with a favorable safety profile. Uses other than in hematologic recovery are less-well studied; more data are needed on immune-enhancing benefits. We envision significantly expanded use of sargramostim in varied immune settings. Sargramostim has the potential to reverse the immune suppression associated with sepsis, trauma, acute respiratory distress syndrome (ARDS) and COVID-19. Further, sargramostim therapy has been promising in the adjuvant setting with vaccines and for anti-microbial-resistant infections and treating autoimmune pulmonary alveolar proteinosis and gastrointestinal, peripheral arterial and neuro-inflammatory diseases. It also may be useful as an adjuvant in anti-cancer immunotherapy.

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“…Hematologic diseases are a heterogeneous group of malignancies that affect people worldwide such as leukemia, lymphoma, and multiple myelomas . In the last two decades, treatment of hematologic malignancy has changed dramatically from chemotherapy to targeted agents such as monoclonal antibodies, small molecule inhibitors, and immunotherapy. , …”

Section: Introductionmentioning

confidence: 99%

“…4 In the last two decades, treatment of hematologic malignancy has changed dramatically from chemotherapy to targeted agents such as monoclonal antibodies, small molecule inhibitors, and immunotherapy. 5,6 Uncontrolled proliferation and gene dysregulation are two hallmarks of cancer, and they are partly regulated by cyclindependent kinase (CDK). These serine−threonine kinases are usually overexpressed in many malignant tumors, which makes them attractive therapeutic targets.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies

et al. 2021

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Hematologic malignancies (HM) start in blood forming tissue or in the cells of the immune system. Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them control cellular transcription. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies. Herein, we describe our efforts toward the discovery of a novel series of quinazoline derivatives as CDK inhibitors. Intensive structural modifications lead to the identification of compound 37d as the most active inhibitors of CDKs 1, 2, 4, 8 and 9 with balancing potency and selectivity against CDKs. Further biological studies revealed that compound 37d can arrest the cell cycle and induce apoptosis via activating PARP and caspase 3. More importantly, compound 37d showed good antitumor efficacy in multiple HM mice xenograft models with no obvious toxicity. These results indicated that CDK 1, 2, 4, 8, and 9 inhibitors could be potentially used to treat certain hematologic malignancies.

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Casting a wider protective net: Anti-infective vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation

Cited by 4 publications

References 183 publications

Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Sargramostim (rhu GM-CSF) as Cancer Therapy (Systematic Review) and An Immunomodulator. A Drug Before Its Time?

Discovery of N-(4-(3-isopropyl-2-methyl-2H-indazol-5-yl)pyrimidin-2-yl)-4-(4-methylpiperazin-1-yl)quinazolin-7-amine as a Novel, Potent, and Oral Cyclin-Dependent Kinase Inhibitor against Haematological Malignancies

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