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A Novel Formulation Strategy to Deliver Combined DNA and VLP Based HPV Vaccine.

Human papillomaviruses (HPV) are small, double-stranded DNA viruses that cause cervical cancer, the second most lethal cancer among women in the world. Currently, two vaccines are on the market for preventing HPV-caused cervical cancers and warts. Both are virus-like particle (VLP)-based vaccines. However, these vaccines have limitations; they are costly, have an invasive route of administration, require trained personnel to administer, need cold chain storage to preserve them, and most of all, they are preventive vaccines that do not have curative effects. Therefore, it is necessary to develo

[Vaccines for the future].

The field of vaccines and vaccinology has seen remarkable progress during the past 20 years. Many vaccines, however, still need to be improved, either because the protection they provide is relatively short-lived and would greatly benefit from the development of booster formulations (as is the case for tuberculosis), or because they only cover part of the many serotypes of the pathogen that causes the disease (rotaviruses, papillomaviruses, or Streptococcus pneumoniae). In addition, still many diseases lack a proper preventive vaccine, such as AIDS, hepatitis C, malaria, viral pneumonias, crou

Current progress in developing mRNA-lipid nanoparticle vaccines against human bacterial pathogens.

SUMMARYThe messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine platform is the newest tool in the vaccination arsenal for combating infectious diseases, rare genetic diseases, and cancer. Since 2020, major advances in preclinical and clinical studies have demonstrated the efficacy of mRNA-LNP vaccines against viral pathogens and in cancer. However, studies investigating the efficacy of mRNA-LNP vaccines against bacterial pathogens remain sparse due to substantial bacterial vaccine-specific challenges. Here, we highlight key challenges impeding the development of mRNA-LNP vaccines against hum

Maximizing Efficacy of Cancer Nanovaccines and Immune Cells Landscape in Responders and Non-Responders to Immunotherapy.

Adjuvants, formulations, and processing of tumor antigens (collection, lysis, purification, and oxidation) can affect the therapeutic efficacy of cancer vaccines. To maximize their efficacy, adjuvants and their combinations are investigated to prepare vaccines with whole tumor antigens. By comparing different nano/micro-vaccines, ≤ 400 nm and 2.5 µm, respectively, are identified as their optimal sizes. When used alone, the optimal cancer vaccine cures all or most tumor-bearing mice with melanoma, lung cancer, pancreatic cancer, and melanoma lung metastasis. The landscape of immune cells in the…

PDT combined with Intravesical BCG instillation would form an autovaccine for bladder cancer?

Bladder cancer is the second most common urologic malignancy after prostate cancer. Intravesical BCG as a treatment of superficial bladder cancer (SBC) has been used by urologists for over 30 years. Recently, photodynamic therapy (PDT), which uses a red laser and a photosensitive drug to destroy cancer cells, has been showed encouraging results in SBC treatment. However, BCG and PDT are applied to treatment of SBC alone. Currently, cancer vaccines are made in vitro. Several studies confirmed that tumour cells treated in vitro by PDT can be used for generating potent cancer vaccines, which were…

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various t

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… The review covers the development of mRNA cancer vaccines, including DC mRNA cancer vaccines and direct injection of mRNA cancer vaccines. It also highlights therapeutic considerations and challenges, good manufacturing practice production, and regulatory aspects of mRNA vaccines. … The article also examines the injection routes of mRNA cancer vaccines and provides a clinical overview of mRNA cancer vaccines. …

Personalized nanovaccines for treating solid cancer metastases.

Cancer vaccines have garnered attention as a potential treatment for cancer metastases. Nevertheless, the clinical response rate to vaccines remains < 30%. Nanoparticles stabilize vaccines and improve antigen recognition and presentation, resulting in high tumor penetration or accumulation, effective co-distribution of drugs to the secondary lymphatic system, and adaptable antigen or adjuvant administration. Such vaccine-like nanomedicines have the ability to eradicate the primary tumors as well as to prevent or eliminate metastases. This review examines state-of-the-art nanocarriers developed…

mRNA melanoma vaccine revolution spurred by the COVID-19 pandemic.

The advent of mRNA vaccines represents a significant advance in the field of vaccinology. While several vaccine approaches (mRNA, DNA, recombinant protein, and viral-vectored vaccines) had been investigated at the start of the COVID-19 pandemic, mRNA vaccines quickly gained popularity due to superior immunogenicity at a low dose, strong safety/tolerability profiles, and the possibility of rapid vaccine mass manufacturing and deployment to rural regions. In addition to inducing protective neutralizing antibody responses, mRNA vaccines can also elicit high-magnitude cytotoxic T-cell responses co

Neoadjuvant Endocrine Treatment plus Mammaglobin-A DNA Vaccine Induces Antitumor Immune Responses in the Primary Tumor and Peripheral Blood of Patients with Breast Cancer: Insights from a Phase Ib Clinical Trial.

Tumor-associated antigen (TAA) vaccines are being explored as a strategy to induce antitumor immune responses. Mammaglobin-A (Mam-A) is a TAA expressed in >50% of patients with breast cancer. Previously, we have shown that Mam-A DNA vaccines induce antitumor immune responses in patients with stable metastatic disease. To further evaluate the potential of the Mam-A vaccine, we initiated a phase Ib clinical trial in patients with estrogen receptor-positive breast cancer prior to surgery. Eight patients were assigned to arm 1 (neoadjuvant endocrine therapy alone) and 17 to arm 2 (neoadjuvant endo

RAD001-Adjuvanted Influenza Vaccine Synergizes With Anti-Programmed Cell Death Protein 1 Therapy to Enhance Antitumor Immunity in Programmed Cell Death Ligand 1-Low Murine Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) have transformed lung cancer therapy, but their efficacy is often limited in tumors with low programmed cell death ligand 1 (PD-L1) expression and immunologically "cold" tumor microenvironments. This study aimed to evaluate the safety and therapeutic efficacy of combining a RAD001-adjuvanted influenza vaccine with PD-1 blockade and to explore its immunological mechanisms in a murine lung cancer model. METHODS: C57BL/6 mice bearing Lewis lung carcinoma (LLC) tumors, characterized by low PD-L1 levels (10.2

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR). METHODS: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both s

Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil(®)): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts.

Quadrivalent human papillomavirus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil(®); Silgard(®)) is composed of virus-like particles formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6, 11, 16 and 18. It is indicated for use from the age of 9 years as a two- or three-dose vaccination course over 6 months for the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts caused by the vaccine HPV types. In placebo-controlled trials, quadrivalent HPV vaccine provided high-level protection against infection or disease cause

The impact of new technologies on vaccines.

Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines

Age-appropriate use of human papillomavirus vaccines in the U.S.

Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the contex

T-cell receptor-engineered T-cell therapy using a glypican-3-specific TCR derived from a hepatoblastoma vaccine responder for HLA-A2-positive glypican-3-expressing cancers.

Glypican-3 (GPC3) is highly expressed in most hepatocellular carcinomas (HCCs) and hepatoblastoma, shows minimal expression in non-tumor adult tissues, and is also detected in several other malignancies, making it an ideal target for anticancer immunotherapy. We previously demonstrated in clinical trials that GPC3 peptide vaccination can induce durable antitumor immunity in patients with HCC and pediatric hepatoblastoma and established human leukocyte antigen (HLA)-A∗02:01-restricted GPC3-specific cytotoxic T lymphocyte (CTL) clones. In this study, we isolated high-avidity T-cell receptors (TC

A Novel Heterologous Prime-boost Strategy Using RUTI Vaccine to Improve the Bacillus Calmette-Guérin Response in Non-muscle-invasive Bladder Cancer Patients: Phase 1 RUTIVAC-1 Trial.

Intravesical bacillus Calmette-Guérin (BCG) is the standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC); however, recurrence and progression remain major challenges. To explore a heterologous prime-boost strategy, we conducted the RUTIVAC-1 trial (NCT03191578) to evaluate RUTI, a nonlive vaccine, derived from Mycobacterium tuberculosis, as a systemic primer prior to intravesical BCG in high-risk NMIBC patients. The immunogenicity, safety, and preliminary efficacy of RUTI was evaluated. In this phase 1, randomized, double-blind, placebo-controlled trial, 40 NMIBC patients

A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies.

PURPOSE: Activating T-cell costimulatory receptors is a promising approach for cancer immunotherapy. In preclinical work, adding an OX40 agonist to in situ vaccination with SD101, a TLR9 agonist, was curative in a mouse model of lymphoma. We sought to test this combination in a phase I clinical trial for patients with low-grade B-cell lymphoma. PATIENTS AND METHODS: We treated 14 patients with low-dose radiation, intratumoral SD101, and intratumoral and intravenous BMS986178, an agonistic anti-OX40 antibody. The primary outcome was safety. Secondary outcomes included overall response rate and

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

PURPOSE: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (De

Short-term safety of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine for patients with advanced lung cancer treated with anticancer drugs: A multicenter, prospective, observational study.

BACKGROUND: Since 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become prevalent worldwide. In severe cases, the case fatality rate is high, and vaccine prevention is important. This study evaluated the safety of receiving SARS-CoV-2 vaccine in patients with advanced lung cancer receiving anticancer therapy. METHODS: We prospectively enrolled patients receiving anticancer drugs for advanced lung cancer who planned to receive SARS-CoV-2 vaccination. Early adverse events within 7 days of vaccine injection were evaluated using patient-reported surveys. The chi-square tes

Pembrolizumab plus GX-188E therapeutic DNA vaccine in patients with HPV-16-positive or HPV-18-positive advanced cervical cancer: interim results of a single-arm, phase 2 trial.

BACKGROUND: Survival outcomes for patients with recurrent or advanced cervical cancer are poor. Pembrolizumab has been approved for the treatment of recurrent or metastatic cervical cancer, with an overall response rate of 14·3%. GX-188E vaccination has been shown to induce human papillomavirus (HPV) E6-specific and E7-specific T-cell responses and cervical lesion regression in patients with cervical precancer. We aimed to investigate whether a combination of GX-188E therapeutic DNA vaccine plus pembrolizumab showed antitumour activity against recurrent or advanced cervical cancer. METHODS: I