scholarly journals Immunologic Monitoring of Cellular Responses by Dendritic/Tumor Cell Fusion Vaccines

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Shigeo Koido ◽  
Sadamu Homma ◽  
Akitaka Takahara ◽  
Yoshihisa Namiki ◽  
Hideo Komita ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Solid Tumors ◽  
Cancer Vaccines ◽  
Evaluation Criteria ◽  
Cellular Responses ◽  
Antitumor Activities ◽  
Patients With Cancer ◽  
Rational Development ◽  
Immunologic Monitoring ◽  
Early Effects

Although dendritic cell (DC)- based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell.

Practical consensus recommendations - Current role of immune response evaluation criteria in solid tumors criteria in the management of cancer patients receiving immunotherapy

2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Evaluation Criteria ◽  
Supporting Evidence ◽  
Response Evaluation ◽  
Consensus Recommendation ◽  
Current Role ◽  
New Class ◽  
Response Evaluation Criteria

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.

scholarly journals Imaging Assessment of Tumor Response in the Era of Immunotherapy

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1041
Author(s):  
Jun Nakata ◽  
Kayako Isohashi ◽  
Yoshihiro Oka ◽  
Hiroko Nakajima ◽  
Soyoko Morimoto ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Solid Tumors ◽  
False Positive ◽  
Progressive Disease ◽  
Tumor Response ◽  
Metabolic Response ◽  
Evaluation Criteria ◽  
Emission Tomography ◽  
Response Criteria ◽  
Positron Emission

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

Chemosaturation durch perkutane hepatische Perfusion mit Melphalan bei hepatisch metastasiertem Aderhautmelanom: eine Überlebens- und Sicherheitsanalyse

2021 ◽  
Vol 42 (08) ◽  
pp. 576-584
Author(s):  
Cornelia Lieselotte Angelika Dewald ◽  
Jan B. Hinrichs ◽  
Lena Sophie Becker ◽  
Sabine Maschke ◽  
Timo C. Meine ◽  
...  
Keyword(s):  
Disease Control ◽  
Solid Tumors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Evaluation Criteria ◽  
Progressionsfreies Überleben ◽  
Response Evaluation ◽  
Ischämischer Insult ◽  
Kaplan Meier ◽  
Response Evaluation Criteria

Ziel Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Material und Methoden Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. Ergebnisse 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Schlussfolgerung Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit.

Pre-clinical evaluation of PV-10 for in vitro anti-tumor activity in refractory and high-risk adult solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14544-e14544
Author(s):  
Son Tran ◽  
Satbir Thakur ◽  
Mohit Jain ◽  
Chunfen Zhang ◽  
Aru Narendran
Keyword(s):  
High Risk ◽  
Tumor Cell ◽  
Solid Tumors ◽  
Cell Lines ◽  
Therapeutic Agent ◽  
Intratumoral Injection ◽  
Tumor Cell Lines ◽  
Clinical Testing ◽  
Anti Tumor Activity

e14544 Background: PV-10 (10% rose bengal disodium; 4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein) is a novel therapeutic agent previously shown to have potent anti-tumor activity following intratumoral injection in melanoma and refractory neuroblastoma, and currently is undergoing clinical testing as a single-agent for refractory metastatic neuroendocrine cancer (NCT02693067) and in combination with checkpoint inhibitors for metastatic melanoma (NCT02557321) and metastatic uveal melanoma (NCT00986661). Given the established clinical efficacy of PV-10 in adult melanoma and hepatic cancers via intratumoral injection, there is a need to evaluate the therapeutic potential of PV-10 in high-risk and refractory adult solid tumors via systemic administration. Our study aims to identify the clinical potential of systemically-delivered PV-10 by first generating prerequisite in vitro data for adult malignancies. Methods: Cytotoxicity assays were performed using the Alamar Blue assay to study the effects of PV-10 in vitro 96-hours post-treatment against a panel of adult solid tumor cell lines derived from breast (MCF-7, T-47D, MDA-MB-231), colorectal (HCT-116, LoVo, T-84), head and neck (CAL-27, Detroit-562, FaDu, UM-SCC-1), and testicular (NCC-IT, NTERA-2, TCAM-2) tissues. Light microscopy and Western blotting were used to investigate apoptosis induction and target modulation in tumor cells after PV-10 treatment. Results: In vitro results from our study demonstrate that PV-10 is cytotoxic at pharmacologically relevant concentrations across the indicated cell lines. Specifically, tumor cell lines originating from testicular tissues were highly sensitive to PV-10 treatment (Mean ± SD IC50: 37.5 ± 16.4 µM; n = 3) compared to breast (117.5 ± 71.0 µM; n = 3), colorectal (64.79 µM; n = 3), and head and neck (106.6 ± 29.2 µM; n = 4) cell lines. Western blot analyses showed dose- and time-dependent activation of pro-apoptotic protein markers in caspase-3 and PARP cleavage, indicating drug-induced apoptosis. Conclusions: This study provides the first pre-clinical results of PV-10 as a novel systemically-delivered therapeutic agent for a range of high-risk and refractory adult solid tumors. Data obtained from our in vitro experiments using a broad repertoire of cell lines that represent diverse molecular and phenotypic subtypes of solid tumors in adults can serve as prerequisite pre-clinical data to establish clinical testing in these populations.

scholarly journals P09.03 Hyaluronic acid as a new immunologic adjuvant in cancer: design of effective preventive and therapeutic vaccination strategies for HER2/neu-positive breast tumors

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A28.2-A29
Author(s):  
D Carpanese ◽  
I Montagner ◽  
A Dalla Pietà ◽  
V Rossi ◽  
A Penna ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Cancer Vaccines ◽  
Tumor Regression ◽  
Vaccination Strategy ◽  
Cellular Responses ◽  
List Type ◽  
Therapeutic Vaccination ◽  
Tlr Agonist ◽  
Humoral Responses

BackgroundThe use of proteins as immunogens is attractive for the development of vaccines, but requires efficient adjuvants to overcome their weak immunogenicity. Recently, we investigated the potential of the TLR2/4 agonist hyaluronan (HA) as an immunological adjuvant for protein-based vaccines.1 2 Conjugation of HA to antigens strongly increased their immunogenicity and promoted their rapid translocation to draining lymph nodes, resulting in robust and long-lasting humoral responses.1 On these bases, we investigated the potentiality of HA-based technology in the design of cancer vaccines. To this aim, HA was conjugated to the extracellular domain of rat HER2/neu (rHER2/neu) and validated in the preventive and therapeutic vaccination settings.Materials and MethodsFemale BALB/c or BALB-neuT mice were immunized with rHER2/neu-HA. In vivo depletion of CD4+, CD8+ T and B cells was performed, and sera and spleens were collected to characterized antigen-specific humoral and cellular responses. Vaccinated BALB/c mice were challenged and re-challenged with rHER2/neu-overexpressing TUBO cells to assess the protective or therapeutic activity of rHER2/neu-HA vaccination strategy, as well as immunological memory.ResultsHA performed efficiently as robust and long-lasting humoral (IgG1, IgG2a, and IgG2b) and cellular responses were detected using very low antigen doses and number of boosters. Outstandingly, at 1-year post-vaccination, anti-rHER2/neu specific antibodies showed even improved effector functions (maturation of affinity for the receptor and increased complement-derived cytotoxicity functions). HA vaccination turned out effective in both the prophylactic (100% mice survived) and therapeutic (tumor regression in 2/12 mice) settings, and broke tolerance against rHER2/neu, delaying spontaneous tumor growth in BALB-neuT mice. Both humoral and cellular responses contributed to the success of HA-based vaccination, but CD8+ T cells played only a marginal role.ConclusionsCancer vaccines have not yet achieved significant clinical efficacy due to their poor immunogenicity, and the validation of more effective adjuvants occurred sometimes at the expense of safety. HA combines the unique immunomodulatory features of a TLR agonist with the tolerability of a fully natural polymer, proving to be a promising adjuvant for the creation of effective and safe cancer vaccines with the potential for rapid clinical translation.ReferencesDalla Pietà A, Carpanese D, et al. Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines. Cell Mol Immunol 2021;18(5):1197–1210.Rosato A, Montagner IM, Carpanese D, Dalla Pietà A. Hyaluronic acid as a natural adjuvant for protein and peptide-based vaccines. 30.04.2020. WO/2020/084558, PCT/IB2019/059122.Disclosure InformationD. Carpanese: None. I. Montagner: None. A. Dalla Pietà: None. V. Rossi: None. A. Penna: None. G. Zuccolotto: None. G. Pasut: None. A. Grigoletto: None. A. Rosato: None.

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