Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen-specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo-prepared DC vaccines are superior to in situ-administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.

• Klíčová slova
• costimulation, homing signal, immune adjuvants, polarizing signal, therapeutic cancer vaccines,
• MeSH
• adjuvancia imunologická terapeutické užití   MeSH
• antigeny nádorové imunologie   MeSH
• dendritické buňky imunologie   MeSH
• imunologická tolerance imunologie   MeSH
• imunoterapie * MeSH
• lidé MeSH
• nádory imunologie   patologie   terapie   MeSH
• přirozená imunita účinky léků   MeSH
• protinádorové vakcíny terapeutické užití   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• antigeny nádorové MeSH
• protinádorové vakcíny MeSH

Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic cell-based vaccines on cancer patients. Herewith, we describe the clinical trials of nonsmall cell lung cancer (NSCLC) published in the literature. Although the number of clinical trials and NSCLC patients enrolled in these studies is small, it is possible to conclude that the administration of dendritic cells (DCs) by any route is safe and that a clinical benefit after their administration can be observed. These initial results encourage continued investigation in clinical trials into the benefit of DCs along with different strategies to enhance their immune response in this deadly disease.

• MeSH
• dendritické buňky imunologie   transplantace   MeSH
• imunoterapie metody   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• nádory plic terapie   MeSH
• nemalobuněčný karcinom plic terapie   MeSH
• protinádorové vakcíny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• protinádorové vakcíny MeSH

Dendritic cells (DCs) have received considerable attention as potential targets for the development of novel cancer immunotherapies. However, the clinical efficacy of DC-based vaccines remains suboptimal, largely reflecting local and systemic immunosuppression at baseline. An autologous DC-based vaccine (DCVAC) has recently been shown to improve progression-free survival and overall survival in randomized clinical trials enrolling patients with lung cancer (SLU01, NCT02470468) or ovarian carcinoma (SOV01, NCT02107937), but not metastatic castration-resistant prostate cancer (SP005, NCT02111577), despite a good safety profile across all cohorts. We performed biomolecular and cytofluorometric analyses on peripheral blood samples collected prior to immunotherapy from 1000 patients enrolled in these trials, with the objective of identifying immunological biomarkers that may improve the clinical management of DCVAC-treated patients. Gene signatures reflecting adaptive immunity and T cell activation were associated with favorable disease outcomes and responses to DCVAC in patients with prostate and lung cancer, but not ovarian carcinoma. By contrast, the clinical benefits of DCVAC were more pronounced among patients with ovarian carcinoma exhibiting reduced expression of T cell-associated genes, especially those linked to TH2-like signature and immunosuppressive regulatory T (TREG) cells. Clinical responses to DCVAC were accompanied by signs of antitumor immunity in the peripheral blood. Our findings suggest that circulating signatures of antitumor immunity may provide a useful tool for monitoring the potency of autologous DC-based immunotherapy.

• Klíčová slova
• Cancer immunotherapy, anti-PD-1, circulating biomarkers, epithelial ovarian carcinoma, metastatic castrate-resistant prostate cancer, non-small cell lung carcinoma,
• MeSH
• dendritické buňky metabolismus   MeSH
• epiteliální ovariální karcinom farmakoterapie   MeSH
• lidé MeSH
• nádory plic * farmakoterapie   terapie   MeSH
• nádory vaječníků * genetika   terapie   MeSH
• protinádorové vakcíny * terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• protinádorové vakcíny * MeSH

Human papilloma viruses (HPV) were found to be closely associated with several types of anogenital tumors, particularly with cervical carcinomas (CC). Of more than 100 HPV types characterized until now, 11 have been classified as high-risk types and detected in human tumor tissue by molecular and immunological techniques. Immunological intervention against HPV can be envisaged at two levels, prophylactic and therapeutic. The therapeutic vaccines constructed to counteract tumors which are already developed utilize two nonstructural early proteins coded by HPV, the products of their E6 and E7 oncogenes. These E6/E7 oncoproteins are the only HPV-coded proteins expressed in CC; they are involved in malignant transformation of HPV-infected cells, their presence is necessary for the maintenance of the malignant phenotype of the cells, and their expression correlates with the transforming potential of HPV. Therefore, the E6/E7 oncoproteins are used for the construction of therapeutic vaccines against HPV-associated neoplasms. The purpose of this review is to discuss the results obtained with HPV16 E6/E7 oncoprotein based therapeutic vaccines in animal tumor models, as well as the prospects and limitations of the vaccines.

• MeSH
• dendritické buňky cytologie   virologie   MeSH
• fenotyp MeSH
• karcinom klasifikace   imunologie   virologie   MeSH
• lidé MeSH
• nádory děložního čípku klasifikace   imunologie   virologie   MeSH
• nádory prevence a kontrola   virologie   MeSH
• onkogenní proteiny virové metabolismus   MeSH
• Papillomaviridae metabolismus   MeSH
• Papillomavirus E7 - proteiny MeSH
• peptidy chemie   MeSH
• protinádorové vakcíny * MeSH
• represorové proteiny * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• E6 protein, Human papillomavirus type 16 MeSH Prohlížeč
• oncogene protein E7, Human papillomavirus type 16 MeSH Prohlížeč
• onkogenní proteiny virové MeSH
• Papillomavirus E7 - proteiny MeSH
• peptidy MeSH
• protinádorové vakcíny * MeSH
• represorové proteiny * MeSH

• MeSH
• forkhead transkripční faktory biosyntéza   MeSH
• imunoterapie * MeSH
• lidé MeSH
• lymfocytární deplece * MeSH
• myši MeSH
• protinádorové vakcíny terapeutické užití   MeSH
• regulační T-lymfocyty cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXP3 protein, human MeSH Prohlížeč
• protinádorové vakcíny MeSH

Dendritic cells (DCs) are the most potent professional antigen-presenting cells with exquisite capacity to interact with T cells and initiate their responses; the antigen-presenting capabilities of DCs make them attractive vehicles for the delivery of therapeutic cancer vaccines. The working hypothesis for utilization of DC-based cancer vaccines is that lack of efficient tumour antigen presentation on mature DCs, which is frequently observed in tumour-bearing individuals, can be bypassed by direct loading of DCs with oncoproteins in vitro, thus ensuring the transfer of immunostimulatory peptides on the respective antigen-presenting molecules. To enhance loading of DCs with oncoproteins in vitro and to increase the efficacy of the vaccines, a variety of genetic manipulations have been proposed and shown to be efficient in experimental tumour models. DCs were transfected either with polynucleotides, DNA or RNA, coding for tumour-associated antigens (TAAs), or with DNA encoding immunostimulatory cytokines and co-stimulatory molecules. The delivery of genes coding for antigenic epitopes or other molecules with a recombinant retrovirus, adenovirus, or poxvirus into dendritic cells has also been used for transduction and therapy. As an alternative method for TAA delivery into DCs, fusion of DCs with tumour cells has been utilized and the hybrid cell-based vaccines have been found to be highly therapeutically active, even in cancer patients. The purpose of this review is to summarize the approaches used for making and utilization of the genetically engineered DC-based cancer vaccines, to evaluate the therapeutic results obtained with the vaccines, and to discuss prospects and limitations of the vaccination.

• MeSH
• antigeny nádorové genetika   imunologie   metabolismus   MeSH
• dendritické buňky imunologie   fyziologie   MeSH
• DNA virů genetika   MeSH
• genetické inženýrství metody   MeSH
• genetické vektory MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• myši MeSH
• nádory terapie   MeSH
• polynukleotidy metabolismus   MeSH
• protinádorové vakcíny genetika   imunologie   MeSH
• technika přenosu genů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• DNA virů MeSH
• polynukleotidy MeSH
• protinádorové vakcíny MeSH

It has been found previously that irradiated, IL-2 gene-modified plasmacytoma (X63-m-IL-2) vaccines are more efficient in the therapy of the parental (X63-Ag8.653) plasmacytoma than live plasmacytoma vaccines. In this communication, we have demonstrated that irradiation of murine IL-2-producing plasmacytoma vaccines resulted in upregulation of CD80 molecule expression and IL-2 production. The expression of MHC class I antigens was not altered. The upregulation of the CD80 membrane molecule expression in X63-m-IL-2 cells was higher after irradiation with 150 Gy than after irradiation with 50 Gy. Comparable upregulation of the CD80 molecule expression has also been demonstrated after irradiation of the parental murine X63-Ag8.653 plasmacytoma cells. The results indicate that upregulation of the CD80 molecule expression and enhanced IL-2 production in irradiated X63-m-IL-2 cells was responsible for the higher therapeutic effectiveness of the irradiated plasmacytoma vaccine.

• MeSH
• antigeny CD80 metabolismus   MeSH
• histokompatibilita - antigeny třídy I metabolismus   MeSH
• interleukin-2 biosyntéza   genetika   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované MeSH
• plazmocytom genetika   imunologie   terapie   MeSH
• protinádorové vakcíny genetika   imunologie   účinky záření   MeSH
• upregulace účinky záření   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD80 MeSH
• histokompatibilita - antigeny třídy I MeSH
• interleukin-2 MeSH
• protinádorové vakcíny MeSH

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy.

• Klíčová slova
• cancer, glycosylation, immune system, infection, vaccination,
• MeSH
• COVID-19 * prevence a kontrola   MeSH
• glykokonjugáty terapeutické užití   MeSH
• lidé MeSH
• nádory * prevence a kontrola   MeSH
• polysacharidy terapeutické užití   MeSH
• SARS-CoV-2 MeSH
• vakcíny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glykokonjugáty MeSH
• polysacharidy MeSH
• vakcíny * MeSH

The effect of irradiation on the therapeutic efficacy of IL-2 gene-modified plasmacytoma cells used as a vaccine in the immunotherapy of parental murine plasmacytoma X63-Ag8.653 was examined. Local administration of the IL-2-secreting plasmacytoma irradiated with a dose of 50 Gy inhibited i.p. plasmacytoma growth more effectively than the administration of non-irradiated, live cell vaccines. Whereas the vaccination with the live cell vaccine could substantially prolong the survival of the tumour-bearing mice but did not significantly induce tumour regressions, the irradiated vaccines could substantially increase the number of tumour-free animals. The irradiated vaccines produce higher amounts of IL-2 than the live cell vaccines both in vitro and in vivo. Depletion of CD4+ and CD8+ effector cells with monoclonal antibodies has significantly decreased the effect of the vaccination. It can be concluded that both, CD4+ and CD8+ T lymphocytes are required for effective IL-2 gene therapy of the X63-Ag8.653 plasmacytoma and that the higher effect of the irradiated vaccines is probably due to their higher IL-2 production.

• MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• DNA vakcíny * MeSH
• genetická terapie metody   MeSH
• interleukin-2 biosyntéza   genetika   MeSH
• lymfocytární deplece * MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buňky kultivované účinky záření   MeSH
• plazmocytom imunologie   patologie   terapie   MeSH
• protinádorové vakcíny * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA vakcíny * MeSH
• interleukin-2 MeSH
• protinádorové vakcíny * MeSH

BACKGROUND: Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer. PATIENTS AND METHODS: This multicenter, single-arm, phase 2a study (NCT04405349, registered 26 May 2020) enrolled adult patients with persistent, r/m HPV16-positive cervical cancer. Patients received 3 mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200 mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment. RESULTS: Between June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95% CI 2.2 to n.r.), median progression-free survival was 4.1 months (95% CI 2.1 to 6.2), and median overall survival was 21.3 months (95% CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22/36 (61%). CONCLUSIONS: The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r/m HPV16-positive cervical cancer, especially if PD-L1-positive.

• Klíčová slova
• Cervical Cancer, Immunotherapy,
• MeSH
• DNA vakcíny * aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• infekce papilomavirem virologie   imunologie   komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidský papilomavirus 16 * imunologie   MeSH
• lokální recidiva nádoru MeSH
• metastázy nádorů MeSH
• nádory děložního čípku * farmakoterapie   virologie   MeSH
• senioři MeSH
• vakcíny proti papilomavirům aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• Názvy látek
• atezolizumab MeSH Prohlížeč
• DNA vakcíny * MeSH
• humanizované monoklonální protilátky * MeSH
• vakcíny proti papilomavirům MeSH