I presented a fascinating Nature paper about the potential use of allogenic IgG in cancer immunotherapy.

1. Inflammation Journal Club
October 20th , 2016
Presented by Thi Nguyen

2. Growth of publications about “cancer immunotherapy”
Science 20 December 2013: Vol. 342 no. 6165
http://www.genengnews.com/insight-and-intelligence/cancer-immunotherapy-
2016/77900623/

3. Non-
specific
Specific
Immunotherapy
Passive ActivePassive Active

4. Key observations:
• Even MHC-matched tumor transplants are readily
rejected by host (same as organ transplant).
• CD4+ CD8+ T cells are required for tumor rejection.
• B cell depletion (ab depletion) prevent tumor rejection.

5. Figure 1 (a-f): Tumor binding antibodies initiate rejection of allogeneic tumors
In vivo
In vitro
a/Experiment design
b/Tumor grows in syngeneic host but is
rejected in allogeneic host. The effect is
mediated by CD4+ and CD8+
.
e/ draining LN: mature DC uptake CFSE-
labeled LMP
c+d/
• CD4+ and CD8+ tumor infiltrate Allo> Syn
• Mature DC in Allo> syn
• Myeloid DC in Syn> Allo
f/ No ag uptake by DC in vitro

6. Figure 1 (g-k): Tumor binding antibodies initiate rejection of allogeneic tumors
g/allo IgG and IgM bind to CFSE-LMP,
48h post transplant.
.
j/ B cell depletion in allogeneic host
leads to tumor development.
h/ 24h post transplant- Co-
localization of CFSE and IgG+ IgM
k/
• Adoptive transfer of Allo IgG but not IgM
enable rejection of syngeneic tumor
• FCgR mediated effect

7. Figure 2 (a-d): Allo-IgG-IC are internalized and presented by BMDC and drive
protective immunity in vivo
a/ tumor cell/ lysate incubate with syn/ allo
abs then co-culture with BMDC
b/ allo-immune complexes increases
activation of BMDC
c/ Increased TNF-alpha and IL-12 by BMDC
culture with allo-immune complexes,
overnight.
d/ Increased ag uptake by BMDC culture
with allo-immune complexes, overnight.

8. Figure 2 (e-h): Allo-IgG-IC are internalized and presented by BMDC and drive
protective immunity in vivo
e/ co-localization of MHC-II with immune
complexes.
f/ Increased T cell proliferation by DC loaded
with allo-immune complexes.
g/ Increased TNF-alpha and IL-12 by BMDC
culture with allo-immune complexes,
overnight.
h/ Only Allo-IgG-IC remained tumor free for
a year.

9. Figure 3 (a-d): alloIgG injection in autologous host doesn’t prevent tumor growth
3a/ tumor growth upon PBS or alloIgG
injection.
3b/ TADC is not activated when incubated
with tumour lysate or allo-IgG-IC
3d/ TADC doesn’t activate T cell
proliferation.
3c/ TADC TNFα and IL-12 secretion

10. Figure 3 (e-f): TADCs, but not BMDCs, requires stimulation to respond to alloIgG-IC
3e/ TADC transfer doesn’t help with
tumor rejection ≠ BMDC
3f/ phospho-species in BMDC> TADCs
3g/ TADC need additional stimulus
cocktail

11. Figure 4 (a-e): Injection of tumors in situ with alloantibodies in combination with
CD40 agonists and TNFα induces systemic DC-mediated antitumor immunity.
4a/ Growth of tumors upon intratumoral
injection of alloIgG combined with stimuli.
4b/ mDC and cDC increases IgG binding upon
stimuli.
4c/ TADC increases MHCII and CD86 upon
stimuli, 5 days after treatment.
4d/Adoptive transfer of TADC from treated mice
into naïve mice.
4e/genetically engineered melanoma model

12. Figure 4 (f-i): Injection of tumors in situ with alloantibodies in combination with
CD40 agonists and TNFα induces systemic DC-mediated antitumor immunity.
4f/ orthotopic 4T1 breast tumors with
metastasis: primary site
4g/ orthotopic 4T1 breast tumor: metastasis
4h/ TADCs from lung cancer patients incubated
with CFSE-stained autologous tumor cells
coated with self or alloIgG.
4i/ mesothelioma patients BMDC culture with
self/ allo IgG coated autologous tumor cells