Quantum Vaccinomics for the Generation of the TAMAVAQ personalized neoantigenic vaccines.
The personalized neoantigen vaccines will be prepared based on the analysis of
whole-exome sequencing (WES) and RNA-seq data generated from fresh-frozen tumours or
tumours that will be available as formalin-fixed paraffin-embedded (FFPE) tissue,
obtained at the time of diagnostic resection. WES of normal tissue will be generated from
autologous PBMC DNA. Patient HLA allotype will be assessed using standard class I and
class II PCR-based typing (BWH Tissue Typing Laboratory). Coding mutations will be
identified and personal neoantigens will be predicted based on binding affinity analysis
to individual HLA alleles using class I MHC binding prediction tools with a cut-off of
predicted IC50 < 500 nM for selected epitopes. Quantum Circuit platforms for the
identification of immunological quantum and design of TAMAVAQ's NeoVaccine consisted of
Druggable Immunodominant and Immunogenic Neo-epitopic Peptides will be incorporated in
this clinical study. Candidate and Prioritized Neo-epitopic Peptides are identified using
systems biology integration of omics dataset combined with Big Data analytics and machine
learning. Then, the immunodominant quantized peptide will be identified by using in
silico algorithms and HLA epitope mapping and binding domains involved in each one Glioma
Patient's Drug-DNA-Protein-protein interactions.
This clinical trial provides an AI-QMMM method for the identification and
characterization of neoantigens and outlines the clinical applications of prospective
immunotherapeutic strategies based on neoantigens exploring their current status,
inherent challenges, and clinical translation potential against Glioma medical
conditions.
Enhanced Targeted Therapy**:- The TAMAVAQ vaccine specifically targets neoantigens unique
to glioma cells, potentially leading to a more effective immune response while sparing
healthy cells. This specificity may reduce collateral damage associated with traditional
cancer therapies.
Immune System Activation**:The TAMAVAQ personalized vaccine is designed to stimulate the
patient's immune system, enhancing its ability to recognize and attack glioma cells. This
activation can lead to a more robust and sustained anti-tumor response.
Potential for Long-term Remission**:- By training the immune system to identify and
remember glioma cells, patients may achieve longer-lasting remission rates and a reduced
likelihood of tumor recurrence compared to conventional therapies.**Reduction in Side
Effects**:- Compared to traditional treatments such as chemotherapy and radiation, which
often come with significant side effects, the TAMAVAQ personalized neoantigen vaccine may
result in fewer adverse effects, thereby improving the patient's quality of life.
Personalized Treatment Approach**:- Each TAMAVAQ vaccine is tailored to the individual
patient's tumor profile, potentially increasing the efficacy of the treatment. This
personalization allows for a more precise approach to therapy that aligns with the unique
characteristics of each Glioma patient's cancer.
Opportunities for Combination Therapies**:- The TAMAVAQ vaccine can potentially be used
in conjunction with other treatments (e.g., checkpoint inhibitors, targeted therapies),
enhancing overall treatment effectiveness and providing a multifaceted approach to combat
glioma.**Real-time Monitoring and Adaptation**:- This clinical trial setting allows for
continuous monitoring of patient responses, providing valuable data that can lead to
adaptations in treatment strategies based on observed efficacy and safety profiles.
Contribution to Scientific Knowledge**:- The TAMAVAQ trial can provide critical insights
into the mechanisms of immune responses against gliomas, contributing to the broader
understanding of cancer immunotherapy and paving the way for future
treatments.**Potential for Broader Application**:Success in the glioma trial may lead to
the development of similar personalized vaccines for other cancer types, expanding the
impact of this innovative therapeutic approach.**Patient Empowerment and
Engagement**:Participation in TAMAVAQ clinical trials often empowers patients by
involving them in cutting-edge research, providing them with access to novel therapies
and fostering a sense of hope in their treatment journey.
This TAMAVAQ clinical trial holds substantial potential benefits, ranging from enhanced
targeted therapy and immune activation to improved patient quality of life and
contributions to scientific knowledge. As research progresses, it is essential to
continue evaluating these benefits in conjunction with the associated risks to optimize
treatment strategies for glioma patients.The development of the TAMAVAQ personalized
vaccine represents a novel approach to glioma treatment. This analysis evaluates the
potential risks and benefits associated with conducting a clinical trial for this
innovative therapeutic strategy.
This clinical trial aims to assess the safety, tolerability, and efficacy of a
personalized neoantigenic vaccine designed for patients diagnosed with glioma. The
TAMAVAQ study will involve identifying patient-specific neoantigens from tumor biopsies
and formulating tailored vaccines to stimulate an immune response against glioma cells.
Following surgery, patients will receive conventional radiation therapy administered at
180-200 cGy per fraction daily for five days per week to a total of approximately 60 Gy.
Personalized neoantigen vaccines TAMAVAQ NeoVaccine will be prepared using information
from fresh tumour and normal tissue obtained at the time of diagnostic resection, as
described below. Algorithms and methods based on profiles of sequence motifs,
quantitative matrices (QM), artificial neural networks (ANN), support vector machines
(SVM), quantitative structure activity relationship (QSAR), T-cell major
histocompatibility complex (MHC) class I binding prediction and molecular docking
simulations among others will be combined and used in order to predict and design the
TAMAVAQ NeoVaccine-Drug Product Neo-epitopes. Quantum chemical calculations (IBM Quantum
Studio) will be used to predict the TAMAVAQ NeoVaccine-Drug Product's biological function
and be applied to T-cell receptor interaction with TAMAVAQ NeoVaccine-Drug Product
Peptide/MHC class
- I. A cluster of algorithms is proposed here using semi-empirical
quantum mechanical methods for calculating peptide-MHC class I and II molecules binding
energy for the rational design of T-cell TAMAVAQ NeoVaccine-Drug Product Neo-epitopes
with application in cancer glioma vaccinology.
The vaccine will be administered
subcutaneously at least seven to twelve weeks following completion of external beam
radiotherapy. TAMAVAQ NeoVaccine-Drug Product will be applied before maintenance of TMZ
cycles after completion of chemoradiation therapy (CRT). Beginning on day 14 before the
first maintenance TMZ cycle, patients will receive 7 vaccinations with TAMAVAQ NeoVaccine
drug products during 7 weeks. 20-200 μg per peptide per vial are used followed by two
booster doses eight and sixteen weeks later. For each dose, vaccine will be administered
within six hours of thawing in a non-rotating fashion to one of up to four extremities.
Patients will be repeatedly vaccinated with TAMAVAQ NeoVaccine drug products beginning on
day 33 of the 6 maintenance TMZ cycle. Patients will receive 9 vaccinations within 12
weeks. 20-400 μg per peptide per vial will be used. Concomitant medications deemed
necessary for adequate patient care will be allowed, including concomitant
corticosteroids for symptoms associated with cerebral oedema, but the study vaccine will
be held for patients requiring more than 4 mg per day of dexamethasone within seven days
of vaccine administration. Clinical assessment and monitoring will be delivered by using
the RANO criteria and the Immunotherapy Response Assessment in the Neuro-Oncology
criteria.
Study Design.
- - Type**: Open-label, single-arm, multicenter clinical trial.
- - Phase**: Phases I & II.
- - Duration**: Approximately 24 months (including recruitment, treatment, and
follow-up) Methodology.
Screening Phase (Month 1-2)**:
Recruitment**: Patients will be recruited from participating medical centers and clinics.
Informed Consent**: Obtain informed consent from eligible patients. Screening
Assessments**: Conduct baseline assessments, including medical history, imaging, and
laboratory tests to confirm eligibility.
Vaccine Development Phase (Month 3-5)**:
Tumor Biopsy**: Collect tumor samples from enrolled patients for sequencing and
neoantigen identification.
Neoantigen Identification**: Utilize computational algorithms and laboratory techniques
to identify patient-specific neoantigens.
Vaccine Formulation**: Develop personalized vaccines based on identified neoantigens
tailored to each patient.
Vaccination Phase (Month 6)**:
-**Pre-Vaccination Assessments**: Conduct baseline assessments, including physical
examinations and laboratory tests before vaccine administration.
- - TAMAVAQ Vaccine Administration**: Administer the TAMAVAQ personalized neoantigenic
vaccine via subcutaneous or intradermal injection.
- - Immediate Post-Vaccination Monitoring**: Monitor patients for immediate side effects
and adverse reactions for a specified period following vaccination.
Follow-Up Phase (Month 7-24)**:
Regular Follow-Up Visits**: Schedule follow-up visits at regular intervals (e.g., every
4-6 weeks) to assess patient health, side effects, and immune response.
Adverse Event Monitoring**: Continuously monitor and report any adverse events or serious
adverse events to regulatory authorities.**Imaging and Laboratory Assessments**: Conduct
imaging studies (e.g., MRI) and laboratory tests to evaluate treatment response and tumor
status at designated follow-up intervals.
Quality of Life Assessments**: Administer validated quality of life questionnaires at
baseline and follow-up visits to assess the impact of AI-QMMM designed TAMAVAQ
treatment.**Study Closure (Month 24)**:
Final Patient Assessments**: Conduct final assessments for all participants to evaluate
long-term outcomes and safety.
Data Analysis and Reporting**: Analyze TAMAVAQ trial data and prepare reports for
submission to regulatory authorities and publication in scientific journals.
Feedback and Follow-Up**: Provide TAMAVAQ vaccinated participants with feedback on trial
outcomes and offer continued follow-up care or access to alternative treatments as
needed.
Sample Size
- - Estimated based on expected effect size and power calculations, aiming for
a target enrollment of approximately 50-140 patients to provide adequate statistical
power for the primary and secondary endpoints.
Statistical Analysis.Descriptive Statistics**: To summarize demographic and baseline characteristics.
Efficacy Analysis**: Kaplan-Meier survival curves for progression-free survival (PFS) and
overall survival (OS).
Adverse Events Analysis**: Frequency and severity of adverse events reported according to
NCI CTCAE criteria.
