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- Cancer and Oncology
-
3. Latest advances in the development of CAR & TCR T-cell treatments for solid tumours
- Dr. Else Marit Inderberg
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4. Mode of action of T cells engineered with CAR or TCR for cancer treatment
- Prof. Sebastian Kobold
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5. Immunotherapy: insights from advanced disease
- Dr. Sara M. Tolaney
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6. Recent advances in the field of non-coding RNAs in cancer
- Prof. George Calin
- Dr. Maitri Shah
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7. How tumor-microenvironment interactions drive or inhibit metastasis
- Prof. Isaac P. Witz
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8. A novel cancer therapy to stimulate oncogenic ERK signalling
- Prof. Reiko Sugiura
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9. MRD-driven multiple myeloma treatment: next step forward
- Prof. Ola Landgren
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11. Germinal centre lymphomas: advances in diagnostic and therapeutic intervention
- Dr. Koorosh Korfi
- Prof. Jude Fitzgibbon
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12. Immunotherapy in lung cancer
- Dr. Mark M. Awad
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13. Preservation of fertility in cancer patients: the impact of chemotherapy
- Prof. Kutluk H. Oktay
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15. Solution proposed to a 2000 year old problem in oncology
- Dr. Michael Retsky
- Clinical Practice
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16. Stillbirth: diagnosis, investigation and aftercare
- Prof. Alexander E. P. Heazell
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17. Analyzing the medical relevance of skin care trends
- Prof. Zoe Draelos
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18. Genetic counseling: preconception, prenatal, perinatal
- Prof. Aubrey Milunsky
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19. The past, present & future of ANA testing: history and challenges of ANA
- Prof. Marvin J. Fritzler
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20. The past, present & future of ANA testing: changing bandwidth and future of ANA
- Prof. Marvin J. Fritzler
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22. Mitochondrial diseases: an update
- Dr. Ayesha Saleem
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23. Hemophilia A
- Dr. Snejana Krassova
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26. Recent advances in diagnosis and interventions in ophthalmology
- Dr. Rebecca Kaye
- Prof. Andrew Lotery
- Gastroenterology
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27. Building implantable human liver tissue from pluripotent stem cells
- Prof. David C. Hay
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28. Microbiome therapies to treat gastrointestinal diseases
- Dr. Patricia Bloom
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29. Drug-induced liver injury: importance, epidemiology, and mechanisms of DILI
- Prof. James H. Lewis
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30. Drug-induced liver injury: risk factors and drug development in DILI
- Prof. James H. Lewis
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31. Drug-induced liver injury: HDS, diagnosing, treating and preventing DILI
- Prof. James H. Lewis
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32. An update on the multiple faces of celiac disease
- Prof. Aaron Lerner
- Immunology
-
33. Rac-enhanced CAR immunotherapy: RaceCAR
- Prof. Denise Montell
-
34. Enhancing innate anti-tumour immunity: lessons from virotherapy and STING agonism 1
- Prof. Kevin Harrington
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35. Enhancing innate anti-tumour immunity: lessons from virotherapy and STING agonism 2
- Prof. Kevin Harrington
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36. Drug allergy: new knowledge
- Prof. Mariana C. Castells
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37. Biologics as a treatment strategy in food allergy
- Prof. Sayantani B. Sindher
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38. B cells at the crossroads of autoimmune diseases
- Dr. Xiang Lin
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39. Studying immune responses “one cell at a time”
- Dr. Mir-Farzin Mashreghi
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40. Mathematical modeling in immunology
- Prof. Ruy M. Ribeiro
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41. Therapeutic antibody development
- Prof. Dr. Katja Hanack
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42. Understanding treatment coverage in mass drug administrations
- Dr. Margaret Baker
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43. The thymus and T cell development: a primer
- Prof. Georg Holländer
- Infectious Diseases
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45. The Global Virus Network: collaboration to address pandemic and regional threats
- Prof. Sten H. Vermund
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46. New concepts in the management of CAP: a focus on severe illness - treatment and therapies
- Prof. Michael S. Niederman
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47. New concepts in the management of CAP: a focus on severe illness - MRSA and MDR pathogens
- Prof. Michael S. Niederman
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48. CRISPR-based suppression drives for vector control
- Prof. Andrea Crisanti
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49. HIV cure: harnessing innate and adaptive strategies
- Prof. Luis Montaner
- Cardiovascular, Metabolism & Nutrition
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50. Cow’s milk allergy: the future
- Dr. Carina Venter
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51. Cow's milk allergy: management
- Dr. Carina Venter
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52. Moving from GWAS hits to functional variants
- Prof. Steve Humphries
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53. X-linked hypophosphataemia: genetics, diagnosis and management
- Prof. Thomas O. Carpenter
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54. What is new in type 1 diabetes?
- Prof. Åke Lernmark
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55. Current concepts for the management of patients with osteoporosis
- Dr. Michael Lewiecki
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56. Antibodies to control or prevent type 1 diabetes
- Dr. Robert Hilbrands
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57. Peptide YY (PYY) in obesity and diabetes
- Dr. Nigel Irwin
- Microbiology
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58. Vaccines and the fight against antimicrobial resistance 1
- Dr. Annaliesa S. Anderson
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59. Vaccines and the fight against antimicrobial resistance 2
- Dr. Annaliesa S. Anderson
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60. Vaccines as a weapon against antibiotic resistance
- Dr. Pumtiwitt McCarthy
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61. PathoLive: pathogen detection while sequencing
- Dr. Simon Tausch
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63. Successes and failures with vaccines
- Prof. Stanley Plotkin
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64. Immunology, the microbiome and future perspectives
- Prof. Sheena Cruickshank
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65. Impact of the HPV vaccine programme – a changing landscape
- Dr. Kevin Pollock
- Neurology and Neuroscience
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66. Advances in the diagnosis and treatment of tardive dyskinesia
- Prof. Emeritus Stanley N. Caroff
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67. Cellular therapies for neurological Injuries: bioreactors, potency, and coagulation
- Prof. Charles S. Cox, Jr.
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68. Cardiovascular involvement in Parkinson’s disease
- Dr. David S. Goldstein
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69. Molecular brain imaging (PET) in diseases with dementia
- Prof. Karl Herholz
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70. Current thinking in pain medicine and some thoughts on back pain
- Dr. Nick Hacking
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71. Bioelectronic medicine: immunomodulation by vagus nerve stimulation
- Prof. Paul Peter Tak
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72. Developments & future directions in the management of chronic pain
- Prof. Simon Haroutounian
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73. Deep Brain Stimulation (DBS) neuromodulation for Schizophrenia
- Prof. Judith Gault
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74. Parkinson’s at 200 years: an update on Parkinson’s research in 2017
- Prof. Patrick A. Lewis
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75. Alzheimer's disease: where are we up to?
- Prof. John Hardy
- Pharmaceutical Sciences
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76. Pharmacokinetics, -dynamics and dosing considerations in children
- Prof. Dr. Karel Allegaert
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77. Why in vitro permeation test – and not in vivo?
- Prof. Howard Maibach
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78. The future of plasma-derived medicinal products (PDMP)
- Dr. Daniele Focosi
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79. RNA therapeutics: clinical applications and methods of delivery
- Prof. John P. Cooke
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80. Recent advances in the development of gene delivery technologies
- Dr. Takis Athanasopoulos
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81. Preclinical translation of mesenchymal stem cell therapies
- Dr. Peter Childs
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82. Modulating gene expression to treat diseases
- Dr. Navneet Matharu
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83. Accelerating drug discovery with machine learning and AI
- Dr. Olexandr Isayev
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84. AI and big data in drug discovery
- Mr. Ed Addison
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85. Emerging big data in medicinal chemistry: promiscuity analysis as an example
- Prof. Dr. Jürgen Bajorath
- Dr. Ye Hu
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86. Binding kinetics in drug discovery
- Dr. Rumin Zhang
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87. Modeling of antibody-drug conjugate pharmacokinetics
- Dr. Dhaval K. Shah
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88. Antibody engineering: beginnings to bispecifics and beyond
- Dr. Ian Wilkinson
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89. Current challenges in the design of antibody-drug conjugates
- Prof. L. Nathan Tumey
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90. Inorganic nanostructured interfaces for therapeutic delivery
- Prof. Tejal Desai
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91. Latest development in therapy-related autophagy research
- Dr. Vignir Helgason
- Respiratory Diseases
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92. Respiratory syncytial virus vaccination
- Prof. Peter Openshaw
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93. Advances in gene therapy for respiratory diseases 1
- Prof. John F. Engelhardt
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94. Advances in gene therapy for respiratory diseases 2
- Prof. John F. Engelhardt
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95. Asthma
- Prof. William Busse
- Dr. Amanda McIntyre
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96. New drugs for asthma
- Prof. Peter Barnes
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97. CompEx asthma: a novel composite exacerbation endpoint
- Dr. Carla A. Da Silva
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98. Updates in chronic obstructive pulmonary disease (COPD)
- Dr. Omar S. Usmani
Printable Handouts
Navigable Slide Index
- Introduction
- The Drosophila ovary as a study model
- Anatomy of an egg chamber
- An in vivo model for collective cell migration
- The slow border cells mutant
- Membrane ruffling is regulated by rac
- Rac is required for actin-rich protrusion and cell migration in vivo
- Organ culture and live imaging problem solved
- Local photoactivation of Rac activity in one cell is sufficient to steer the whole cluster
- Focal and transient signal stimulates migration toward a target
- But constitutively active Rac in border cells destroys the whole egg chamber
- A 25-year-old cold case until a clue appeared
- Rac is required for engulfment
- Are RacV12-expressing border cells prematurely eating nurse cells alive?
- But border cells eat neighboring follicle cells instead…
- Active Rac stimulates cells to eat other cells alive
- Patients with a mutation that hyperactivates Rac2 suffer from recurrent infections
- Patients with an activating mutation in Rac2 are immunodeficient because they lack T cells
- Are the patients’ hyperactive phagocytes eating their T cells alive?
- Co-culture macrophages with T cells
- Isolate B and T cells from Rac2E62K/+ mice and littermate controls
- Rac2E62K macrophages hyper engulf Rac2E62K T cells (1)
- Rac2E62K macrophages hyper engulf Rac2E62K T cells (2)
- Is the effect autonomous to macrophages or does Rac2E62K affect the T cells too?
- Rac is downstream of the T-cell receptor
- What does Rac2E62K do to T cells?
- Rac2E62K hyperactivates macrophages and T cells
- CAR-T therapy
- Limitations of CAR-T therapy
- CAR-macrophage: a newer cousin with benefits
- CAR-P/CAR-M cancer immunotherapy
- CAR-M/P macrophages eat B cell lymphoma cancer cells
- Rac-enhanced CAR-M
- Hyperactive Rac enhances CAR-M engulfment and killing
- The effect requires a specific ligand interaction
- Can Rac2E62K macrophages stimulate WT macrophages to eat more?
- Rac-mediated lymphocyte hyper-phagocytosis causes immuno-deficiency
- Weak, focal, transient signal stimulates migration toward a target
- Does RaceCAR work in vivo?
- Does RaceCAR work in ovo?
- Imaging of tumor intravasation
- Imaging of macrophage infiltration of tumor
Topics Covered
- Drosophila egg chamber
- Slow border cells-rac
- CAR-T therapy
- CAR-Macrophage
- Rac-enhanced CAR-M
Links
Series:
- The Legacy of Drosophila Genetics
- Periodic Reports: Advances in Clinical Interventions and Research Platforms
Categories:
Therapeutic Areas:
Talk Citation
Montell, D. (2025, January 30). Rac-enhanced CAR immunotherapy: RaceCAR [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved February 5, 2025, from https://doi.org/10.69645/ZUKB3789.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Denise Montell has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Oncology
Transcript
Please wait while the transcript is being prepared...
0:00
Hi. My name is Denise Montell,
I'm a professor of molecular,
cellular, and developmental biology
at the University of
California in Santa Barbara.
I'm going to tell you
today about a project that
really started out as
fundamental basic cell biology
in the fruit fly
ovary and it took us
entirely unexpectedly into
a potential clinical application
specifically an enhanced
cellular immunotherapy.
0:28
My lab is generally
interested in
how cells behave normally as
they're building and
maintaining tissues and then
how they misbehave in
diseases like cancer.
A dream for us would
be to be able to
harness this knowledge
to treat disease.
For many of our studies,
we use the model shown here
the drosophila ovary because
of the rich diversity
of biological questions
that can be addressed
by the simple and beautiful
anatomy of this tissue,
the powerful experimental tools
available in this organism
and, of course, the long
history of success using
drosophila to solve fundamental
problems in biology.
Now, the ovary as you
see here is composed
of individual strands of
developing egg timbers.
At the tip of each one of
these strands reside stem cells,
two different kinds
of stem cells,
somatic stem cells and
germline stem cells.
And the progeny of
those cells assemble
into these little ovals
called egg chambers
and each egg chamber
grows and develops
into a mature egg,
which you can see near
the center of this
flower-like structure.
1:37
Now if we zoom in on one of
those strands of
developing egg chambers,
the stem cells as
labeled here are
up near the anterior
tip of this structure.
Then the developing egg
chambers are arrayed in
a sort of assembly line fashion
in increasing size as
they grow and mature.
We can see the detailed anatomy
of an egg chamber here where
in the center of
the structure are
16 cells that are germ cells.
One cell the oocyte is the cell
that's going to grow
into the egg itself.
Connected to it are
these giant cells
the nuclei are labeled in
blue here called nurse cells.
And the nurse cells' job is to
nourish the oocytes by providing
it with the cytoplasm.
Surrounding the nurse cells
and oocytes are
the somatic cells.
And we can see that
most of them stack up
in a columnar layer in
contact with the oocyte.
Leaving a few cells
to spread out in
this thin squamous layer around
covering the nurse cells.
Now a group of cells
that my lab has
been interested in
for some time starts
out as part of this epithelium
when all the cells are
more or less the
same cuboidal shape.
But then as the reorganization
occurs where most
of the cells are
stacking up in a columnar
epithelium and some of
them are stretching out into
this thin squamous layer,
the border cells actually detach
from the epithelium entirely
and migrate in between
the nurse cells.
They squeeze in between
the nurse cells
until they reach the anterior
border of the oocyte,
which is why they were
named border cells.